Benzyl Bromide → 3(R)-Benzyl-5(S)-[5-benzyloxy-1(S)-tert-butoxycarbonylamino-3,3-dimethyl-pentyl]-2-oxotetrahydrofuran

HRID 863271Notes

Reaction equation

HRID 863271 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11]([CH3:29])([CH3:28])[CH2:12][C@@H:13]([C@H:22]1[O:26][C:25](=[O:27])[CH2:24][CH2:23]1)[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:40](Br)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>O1CCCC1>[CH2:40]([C@@H:24]1[CH2:23][C@@H:22]([C@@H:13]([NH:14][C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[CH2:12][C:11]([CH3:29])([CH3:28])[CH2:10][CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[O:26][C:25]1=[O:27])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 2733832Lithium HexamethyldisilazideHCID 867521045(S)-[5-Benzyloxy-1(S)-tert-butoxycarbonylamino-3,3-dimethyl-pentyl]-2-oxotetrahydrofuran

Product 1

HCID 676254563(R)-Benzyl-5(S)-[5-benzyloxy-1(S)-tert-butoxycarbonylamino-3,3-dimethyl-pentyl]-2-oxotetrahydrofuran

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of 1.76 g of 5(S)-[5-benzyloxy-1(S)-tert-butoxycarbonylamino-3,3-dimethylpentyl]-2-oxo-tetrahydrofuran in 30 ml of tetrahydrofuran is added to a mixture of 9.14 ml of a 1M lithiumbis(trimethylsilyl)amide solution in tetrahydrofuran and 30 ml of tetrahydrofuran at -78° C. under argon and the mixture is stirred for 30 min. 0.63 ml of benzyl bromide in 30 ml of tetrahydrofuran are then added dropwise. After the mixture has been stirred at -78° C. for 3.5 h, the reaction is quenched by addition of 1.6 ml of propionic acid and the mixture is diluted with diethyl ether. The organic phase is washed with a 10% aqueous citric acid solution and a 1M sodium bicarbonate solution, dried over sodium sulfate and concentrated. Purification over silica gel (mobile phase D) gives the title compound: Rf (D)=0.23; FAB-MS: (M+H)+ =496.

Workup

  1. stirringAfter the mixture has been stirred at -78° C. for 3.5 h
  2. customthe reaction is quenched by addition of 1.6 ml of propionic acid
  3. additionthe mixture is diluted with diethyl ether
  4. washThe organic phase is washed with a 10% aqueous citric acid solution
  5. dry with materiala 1M sodium bicarbonate solution, dried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification over silica gel (mobile phase D)

Sources & evidence

ORD record
ord-71cb43efcd514b0a8aa336b0c4968d9d
Source dataset
uspto-grants-1998_02
Patent number
US05719141

Reaction notes

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