Ammonium Chloride → (S)-1-(tert-Butoxycarbonyl)-2-[1-hydroxy-4-(phenylmethyloxy)butyl]pyrrolidine

HRID 1735412Notes

Reaction equation

HRID 1735412 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH:10]=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH2:21][O:22][CH2:23][CH2:24][CH2:25][Mg]Cl)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.ClCCCOCC1C=CC=CC=1.[Cl-].[NH4+]>O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH:10]([OH:11])[CH2:25][CH2:24][CH2:23][O:22][CH2:21][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 221505((3-Chloropropoxy)methyl)benzeneHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylateHCID 178479006HCID 178479006, compound

Product 1

HCID 67745428(S)-1-(tert-Butoxycarbonyl)-2-[1-hydroxy-4-(phenylmethyloxy)butyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A THF solution (20 ml) of N-(tert-butoxycarbonyl)-L-prolinal (4.50 g) was dropwise added to a THF solution (30 ml) of 3-(phenylmethyloxy)propyl magnesium chloride prepared from 1-chloro- 3-(phenylmethyloxy)propane (5.00 g), at -78° C. After stirring for 15 minutes, saturated ammonium chloride (10 ml) was added, and the reaction mixture was allowed to reach room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with 10% citric acid, saturated sodium hydrogencarbonate and saturated brine in order, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography (eluent: n-hexane-ethyl acetate) to give two stereoisomers (1.89 g of low polar isomer and 3.05 g of high polar isomer).

Workup

  1. customto reach room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with 10% citric acid, saturated sodium hydrogencarbonate and saturated brine in order
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customto give two stereoisomers (1.89 g of low polar isomer and 3.05 g of high polar isomer)

Sources & evidence

ORD record
ord-7a5ed88829104f14b9fc010cc455a791
Source dataset
uspto-grants-1996_07
Patent number
US05536737

Reaction notes

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