Pyridine, hydrofluoride (1:1) → 3-Fluoro-3-(1-hydroxyethyl)pyrrolidine-1-carboxylic acid benzyl ester

HRID 729438Notes

Reaction equation

HRID 729438 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:18][CH2:17][C:13]2([O:15][CH:14]2[CH3:16])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[FH:25]>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:18][CH2:17][C:13]([F:25])([CH:14]([OH:15])[CH3:16])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 21041146Benzyl 2-methyl-1-oxa-5-azaspiro[2.4]heptane-5-carboxylate

Product 1

HCID 690767793-Fluoro-3-(1-hydroxyethyl)pyrrolidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.247 g, (1 mmol) of 2-methyl-1-oxa-5-azaspiro[2,4]-heptane-5-carboxylic acid benzyl ester (Example A9) in dichloromethane (3 mL) is added to a polypropylene flask containing 0.5 mL of hydrogen fluoride-pyridine at −40° C. The reaction is allowed to come to room temperature and stirring is continued for 3 hours. The reaction mixture is poured into an aqueous ice-cold ammonium hydroxide solution (30 mL) and extracted with dichloromethane. The organic layer is dried, filtered and concentrated to afford the title compound (0.267 g). 1H NMR (200 MHz, CDCl3): δ 7.35 (s, 5H), 5.13 (s, 2H), 3.96-3.34 (m, 5H), 2.20-1.98 (m, 3H), 1.33-1.26 (m, 3H).

Workup

  1. customto come to room temperature
  2. extractionextracted with dichloromethane
  3. customThe organic layer is dried
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-577a9d99335d4e37b77697de7096da36
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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