Ammonia → (2S,4R)-1-Boc-2-carbamoyl-4-hydroxypyrrolidine

HRID 1873524Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:19](CC)CC)C.ClC(OCC)=O.N.[Cl-].[NH4+]>O1CCCC1>[C:14]([C@@H:9]1[CH2:10][C@@H:11]([OH:13])[CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])(=[O:16])[NH2:19]

Participants

Conditions

Temperature: -15 °C

Procedure

(2S,4R)-1-(tert-Butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 13b (86.4 g, 0.374 mol) was dissolved in 1.2 L of tetrahydrofuran followed by addition of triethylamine (41 g, 0.411 mol) under argon atmosphere. The reaction mixture was cooled to −15° C., ethyl chlorformate (43.84 g, 0.411 mol) was added. After the mixture was stirred for 10 minutes, aqueous ammonia (236.8 mL) was added. The reaction mixture was slowly warmed up to 5° C. during 2 hours followed by addition of ammonium chloride (32 g). The reaction mixture was stirred for 30 minutes and separated. The separated organic phase was dried over anhydrous sodium sulfate, and the aqueous phase was extracted with ethyl acetate (100 mL×2). The combined organic extracts were concentrated under reduced pressure to obtain the title compound (2S,4R)-tert-butyl 2-carbamoyl-4-hydroxypyrrolidine-1-carboxylate 13c (74 g, yield 86%) as a white solid.

Workup

temperatureThe reaction mixture was slowly warmed up to 5° C. during 2 hours
stirringThe reaction mixture was stirred for 30 minutes
customseparated
dry with materialThe separated organic phase was dried over anhydrous sodium sulfate
extractionthe aqueous phase was extracted with ethyl acetate (100 mL×2)
concentrationThe combined organic extracts were concentrated under reduced pressure

Sources & evidence

ORD record: ord-056d2b9a01e04737914c2b5a8787633d
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304411B2

Reaction notes

Loading…