Bromotrimethylsilane → (S)-4-Azido-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline, methyl ester

HRID 851430Notes

Reaction equation

HRID 851430 reaction equation
[N:1]([CH:4]1[CH2:8][N:7]([C:9](=[O:26])[CH2:10][P:11]([O:23]CC)([CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:12])[C@H:6]([C:27]([O:29][CH3:30])=[O:28])[CH2:5]1)=[N+:2]=[N-:3].Br[Si](C)(C)C>ClCCl>[N:1]([CH:4]1[CH2:8][N:7]([C:9](=[O:26])[CH2:10][P:11]([OH:23])([CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:12])[C@H:6]([C:27]([O:29][CH3:30])=[O:28])[CH2:5]1)=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 131712758(S)-4-Azido-1-[[ethoxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline, methyl ester

Product 1

HCID 131712759(S)-4-Azido-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline, methyl esterYield 90.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-4-Azido-1-[[ethoxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline, methyl ester (1.60 g), dry dichloromethane and bromotrimethylsilane (0.85 g) are stirred under argon at room temperature. After 19 hours, an additional equivalent of bromotrimethylsilane is added and stirring is continued for 2 hours. Excess bromotrimethylsilane and dichloromethane is removed in vacuo and the residue is treated with ethyl acetate/water and stirred for 15 minutes. The layers are separated and the ethyl acetate layer is extracted with saturated sodium bicarbonate. The aqueous extracts are acidified to pH 1.0 with concentrated hydrochloric acid and extracted with ethyl acetate. The extract is washed with water, brine, dried over sodium sulfate, and the solvent stripped to yield 1.35 g of the title compound as an oil.

Workup

  1. waitis continued for 2 hours
  2. customExcess bromotrimethylsilane and dichloromethane is removed in vacuo
  3. additionthe residue is treated with ethyl acetate/water
  4. stirringstirred for 15 minutes
  5. customThe layers are separated
  6. extractionthe ethyl acetate layer is extracted with saturated sodium bicarbonate
  7. extractionextracted with ethyl acetate
  8. washThe extract is washed with water, brine
  9. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-2cd0f03cd8534667b25ef4a76907c2a7
Source dataset
uspto-grants-1983_05
Patent number
US04384123

Reaction notes

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