Benzylamine → (3S)-1-benzyl-4,4-dimethyl-3-pyrrolidinol

HRID 750393Notes

Reaction equation

HRID 750393 reaction equation
CS(O[CH2:6][C@@H:7]([OH:17])[C:8]([CH3:16])([CH3:15])[CH2:9]OS(C)(=O)=O)(=O)=O.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)C>[CH2:18]([N:25]1[CH2:9][C:8]([CH3:16])([CH3:15])[C@H:7]([OH:17])[CH2:6]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 58981714(2S)-2-hydroxy-3,3-dimethyl-4-[(methylsulfonyl)oxy]butyl methanesulfonate

Product 1

HCID 10442950(3S)-1-benzyl-4,4-dimethyl-3-pyrrolidinolYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 21.7 g (75 mmol) of (2S)-2-hydroxy-3,3-dimethyl-4-[(methylsulfonyl)oxy]butyl methanesulfonate and 24.4 mL (228 mmol) of benzylamine in 200 mL of ethanol was heated at 120° C. for 18 h in a 400 mL capacity bomb. The reaction mixture was allowed to cool to room temperature, the bomb was vented, and the reaction mixture was concentrated under reduced pressure to 100 mL. The reaction was diluted with 50 mL of water and made acidic with concentrated hydrochloric acid. The aqueous phase was then washed with ether, made basic with 5M aqueous sodium hydroxide, and extracted with ether. The ether extract was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0.25:9.75 2M ammonia in methanol:ethyl acetate to afford 13.8 g (90%) of (3S)-1-benzyl-4,4-dimethyl-3-pyrrolidinol. 1H NMR (300 MHz, CDCl3) δ 7.30-7.36 (m, 5H), 3.77 (br s, 1H), 3.65 (s, 2H), 2.93-2.99 (m, 1H), 2.55-2.64 (m, 2H), 2.31 (d, J=9 Hz, 1H), 1.76 (d, J=7 Hz, 1H), 1.09 (d, J=1 Hz, 6H).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure to 100 mL
  2. additionThe reaction was diluted with 50 mL of water
  3. washThe aqueous phase was then washed with ether
  4. extractionextracted with ether
  5. extractionThe ether extract
  6. concentrationwas concentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography
  8. washeluting with 0.25:9.75 2M ammonia in methanol

Sources & evidence

ORD record
ord-4ba3ca39122145feb154cf229551b631
Source dataset
uspto-grants-2008_07
Patent number
US07402606B2

Reaction notes

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