3-Fluorobenzyl bromide → 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-(m-fluorophenylmethyl)-dihydrofuran-2-(3H)-one

HRID 263784Notes

Reaction equation

HRID 263784 reaction equation
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37]Br.CCCCCC.C(OCC)(=O)C>C1COCC1>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:37][C:36]2[CH:39]=[CH:40][CH:41]=[C:34]([F:33])[CH:35]=2)[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 680073-Fluorobenzyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 21226206Ethyl acetate hexane

Product 1

HCID 677187205(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-(m-fluorophenylmethyl)-dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Analogously to Example 21 D) 1)c), 5.0 g (16.37 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-dihydrofuran-2-(3H)-one [Example 21 D) 1)b)] dissolved in 75 ml of THF are deprotonated at -75° C. with 32.7 ml of lithium bis(trimethylsilyl)amide 1M in THF and alkylated starting at -75° C. with 3.4 g (18.0 mmol) of 3-fluorobenzyl bromide (Fluka; Buchs/Switzerland) (warming up during 60 min up to max. -50° C.). Column chromatography (SiO2, hexane/ethyl acetate 3:1) yields the title compound: TLC Rf (D)=0.6; tRet (I)=17.2 min.

Workup

  1. temperaturewarming up during 60 min up
  2. custom-50° C.

Sources & evidence

ORD record
ord-9f41d5bdadeb47a383a7f39bdcf9df1a
Source dataset
uspto-grants-1997_07
Patent number
US05643878

Reaction notes

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