Sodium Hydroxide → 1-((S)-1-benzylpyrrolidin-2-yl)cyclopropanol

HRID 734775Notes

Reaction equation

HRID 734775 reaction equation
[CH2:1]([Mg]Br)[CH3:2].C(O[C:8](=[O:21])[C@@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)C.[OH-].[Na+]>C(OCC)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH2:14]([N:10]1[CH2:11][CH2:12][CH2:13][C@H:9]1[C:8]1([OH:21])[CH2:2][CH2:1]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 688177N-Benzyl-L-proline ethyl esterHCID 178418443HCID 178418443, compound

Product 1

HCID 690581421-((S)-1-benzylpyrrolidin-2-yl)cyclopropanol

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-15 °C

Procedure

First 6.91 mL (23.57 mmol) of titanium (IV) isopropoxide and then 14.3 mL (42.9 mmol, 3 M in diethyl ether) of ethylmagnesium bromide were slowly added dropwise to a solution of 5.0 g (21.43 mmol) of N-benzyl-L-proline ethyl ester in 80 mL of dry diethyl ether which had been cooled to −15° C. and the reaction mixture was stirred for 30 minutes at this temperature. Subsequently at approximately 10° C., 5.4 mL (42.9 mmol) of boron trifluoride-diethyl ether complex were added and the mixture was stirred for a further 75 hours at RT. While cooling, 50 mL of 1M NaOH was added, the mixture was stirred for 1 hours at RT, combined with 100 mL of diethyl ether, and the organic phase was separated off and dried over sodium sulfate. After the desiccant and solvent had been eliminated, the residue was purified by chromatography (silica gel, EtOAc). Yield: 0.745 g (16% of theoretical); C14H19NO (M=217.307); calc.: molpeak (M+H)+: 218; found: molpeak (M+H)+: 218; Rf value: 0.17 (silica gel, EtOAc).

Workup

  1. additionSubsequently at approximately 10° C., 5.4 mL (42.9 mmol) of boron trifluoride-diethyl ether complex were added
  2. stirringthe mixture was stirred for a further 75 hours at RT
  3. temperatureWhile cooling
  4. stirringthe mixture was stirred for 1 hours at RT
  5. customthe organic phase was separated off
  6. dry with materialdried over sodium sulfate
  7. customthe residue was purified by chromatography (silica gel, EtOAc)

Sources & evidence

ORD record
ord-fab0ef437fc64a3ca983929e4aef59eb
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

Loading…