Product Usage 1-tert-butoxycarbonyl-3-pyrrolidone is a starting material and a useful intermediate in organic synthesis.

1. Description
Brown Oil
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Basic Attributes
CAS No：101385-93-7
Molecular Formula ：C9H15NO3
Molecular Mass ：185.22
Exact Mass ：185.105194
PSA ：46.6 A^2
LogP ：0.7
EINECS ：1308068-626-2
InChIKeys ：JSOMVCDXPUXKIC-UHFFFAOYSA-N
H-bond Acceptor ：3
H-bond Donor ：0
SP3 ：0.78
RBN ：2
Characteristics
Appearance ：White to yellow to orange Low Melting Solid
Density ：1.133±0.06 g/cm3(Predicted)
Melting Point ：34-38 °C(lit.)
Bolling Point ：270.9±33.0 °C(Predicted)
Flash Point ：>230 °F
Refractive Index ：1.486
Solubility ：Insoluble in water.

2. Storage Condition ：Store at 0-5°C
Safety Information
HS Code ：29339900
UN No. ：NONH for all modes of transport
WGK_Germany ：3
Risk Code ：22-37/38-41-36/37/38-20/21/22
Safety Instructions ：26-36/37/39-36
Dangerous Mark ：Xn,Xi
P Code ：P261-P280-P305 + P351 + P338
Hazard Statements ：H302-H315-H318-H335
Hazard Note ：Irritant
Product Usage
1-tert-butoxycarbonyl-3-pyrrolidone is a starting material and a useful intermediate in organic
synthesis.
Production Methods
To a cold (-78° C.) solution of oxalyl chloride (2.8 mL, 32.4 mmol) in CH[0356] Part A: To a

3. solution of oxalyl chloride (1.3 mL, 15 mmol) in 20 mL of dichloromethane at -60° C. was added
methyl sulfoxide dropwise over period of 10 min. After stirring at -60 ° C., a solution of
1,1-dimethylethyl 3-hydroxypyrrolidine-1-carboxylate (1.87 g, 10 mmol) in 20 mL of
dichloromethane was added over 20 min. Then, diisopropylethylamine (8.8 mL, 50 mmol) was
added over 5 min. The resulting mixture was stirred at -60 ° C. for 25 min, and at room
temperature for 30 min. The reaction was diluted with dichloromethane (100 mL). The organic
layer was washed sequentially with saturated sodium bisulfate solution (2.x.), saturated sodium
bicarbonate solution, water, and brine; dried over sodium sulfate; and concentrated to afford 1.8
g (97percent) of 1,1-dimethylethyl 3-oxo-pyrrolidine-1-carboxylate: 1H-NMR (CDCl3) δ 3.75 (4H,
m), 2.58 (2H, t, J=7.8 Hz), 1.49 (9H, s).To a solution of 3-hydroxy-pyrrolidine-1-carboxylic acid
tert-bxty ester (10 g, 54 mmol) in dichloromethane (300 mL) is added Dess-Martin Reagent
(45.9 g, 108 mmol) in three portions. The resulting mixture is stirred for 16 hours. The mixture is
filtered through CeIi te and the solvent removed in vacuo. The crude material is purified via silica
gel chromatography using a gradient elution of 0-8percent ethyl acetate/hexanes to afford the
desired product as a glassy solid (9.8 g, 97percent).A 3 L, four-necked round-bottomed flask was
equipped with a mechanical stirrer, 500 mL addition funnel, cooling bath, K-type thermocouple
and a nitrogen inlet. Oxalyl chloride (6.0 mL, 70.5 mmol) was added to 300 mL of DCM and
cooled to - 78°C. DMSO (9.9 mL, 139mmol) was added thereto, and the mixture was stirred for
15 minutes. tert-butyl 3-hydroxypyrrolidin-1-carboxylate (8.98g, 48 mmol) obtained in Step A was
added thereto, and the mixture was stirred for 20 minutes. TEA (32 mL, 0.23 mol)was added
thereto, and the mixture was stirred at -78 ° C for 1 hour and addtionally stirred at room
temperature for 1hour. After addition of water, the reaction solution was extracted with DCM.
The organic layer was dried with MgSO4and purified by column chromatography to obtain the
title compound (7.92 g, 89 percent).1H-NMR (CDCl3) δ 3.77 (4H, m), 2.59 (2H, t), 1.48 (9H,
s)N-Boc-3-pyrrolidinol (17.192 g, 0.092 mole) in 50 mL anhydrous methylene chloride was added
to a solution of (60 g, 0.276 mole) of pyridinechlorochromate in 300 mL anhydrous methylene
chloride which was surrounded by a water bath at room temperature. After stirring at room
temperature for 4 hours an additional (60 g, 0.276 mole) of pyridinechlorochromate was added
and the reaction was stirred over night. The reaction had gone to completion by the next
morning and was diluted with 400 mL diethyl ether and filtered through a pad of celite 521 filter
aid using excess diethyl ether to wash through. Evaporation gave a black oil which was flash
chromatographed over silica gel eluting with 40percent ethyl acetate in hexane to provide the
title compound (12.5 g, 71percent) as an oil. a) 3-Oxo-pyrrolidine-l-carboxylic acid tert-butyl ester
In a 1 1 three-necked flask, 10 g of N-Boc-3- hydroxypyrrolidine are dissolved in 350 ml of
dimethyl sulphoxide in the presence of 52.3 ml of triethylamine . 28 g of pyridine-sulphur trioxide
complex dissolved in 350 ml of dimethyl sulphoxide are added dropwise to the above solution.
The reaction mixture is stirred for 4 hours at ambient temperature. The reaction medium is
acidified to pH 4.5-5 with a IM solution of hydrochloric acid and the reaction mixture is then
extracted with ethyl acetate. The organic phases are combined and then dried over anhydrous
sodium sulphate. The residue is filtered through silica gel (1/1 heptane/ethyl acetate) . 5.7 g of
3-oxo-pyrrolidine-l- carboxylic acid tert-butyl ester are obtained. Yield: 58percent.Pyridinium
chlorochromate (481 mmol) was added to a solution of tert-butyl
3-hydroxypyrrolidine-1-carboxylate (160 mmol) in dichloromethane (800 mL) and the reaction
mixture was maintained at rt for 16 h. The insoluble solids were removed by filtration and the

4. filtrate was concentrated. The residue was purified by Flash chromatography (20/1 to 10/1
petroleum ether/ethyl acetate) to provide tert-butyl 3-oxopyrrolidine-1-carboxylate in 51percent
yield as light yellow oil.To a stirred solution of tert-butyl (R)-3-hydroxypyrrolidine-l-carboxylate
(Intermediate 8-step 1, 4.5 g, 24.1 mmol) in DCM (60 ml) under NTo a stirred solution of
tert-butyl (R)-3-hydroxypyrrolidine-1-carboxylate (4.5 g, 24.1 mmol) in DCM (60 ml) under N1)
N-tert-Butoxycarbonyl-3-pyrrolidinone Pyridine-sulfur trioxide (4.12 g) was added to a solution of
(3R)-N-tert-butoxycarbonyl-3-hydroxypyrrolidine (2.47 g) and triethylamine (9.19 mL) in
dimethylsulfoxide (30 mL) at room temperature, and the resultant mixture was stirred overnight.
The reaction solution was poured onto water and extracted with diethyl ether. The organic layer
was washed with water and saturated saline, and then dried over anhydrous sodium sulfate.
After separation by filtration, a residue obtained by evaporating the solvent under reduced
pressure was purified by silica gel column chromatography (ethyl acetate-hexane), to obtain
N-tert-butoxycarbonyl-3-pyrrolidinone (855 mg, 34percent) as an oily product. b) tert-Butyl
3-oxopyrroIidine-l-carboxylate; To a solution of step a) product (10 g, 0.053 mol) in dry CHEthyl
N-Boc pyrrolidonecarboxylate (20.0 g) (compound of formula (II) wherein R is Et) was dissolved in
toluene (30 ml) and dimethylsulfoxide Mixture and 20 mg of 3,5-di-tert-butyl-4-hydroxytoluene
(BHT) was added.The resulting mixture was heated to 115 ° C (internal temperature) and
water (4.2 ml, 3.0 eq) was added dropwise over 5 h maintaining the internal temperature at
110-115 ° C.The desired conversion was achieved 1 hour after the water addition was
completed.The reaction mixture was cooled to 20 ° C and diluted with water (10 ml).The layers
were separated and the aqueous layer re-extracted with toluene (20 ml).The combined organic
layers were washed with 20 ml of 5percent w / w aqueous NaCl and then with 10percent w / w
NaCl (40 ml) and finally with 20 ml of water.The resulting toluene solution was treated with
activated carbon.After filtration, the filtrate was concentrated to dryness to give an orange oil (14
g).Cyclohexane (12 ml) was added at -5 / -10 ° C and the resulting suspension was filtered and
washed twice with 3.5 ml of cyclohexane.The solid was dried under vacuum in a 25 ° C oven to
give 10.8 g of a white solidbody.The molar yield after separation was 75percent.