alpha-Bromo-o-fluorotoluene → 5(S)[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(o-fluorophenyl)methyl]dihydrofuran-2-(3H)-one

HRID 2394087Notes

Reaction equation

HRID 2394087 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:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36]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]([CH2:36][C:35]2[CH:38]=[CH:39][CH:40]=[CH:41][C:34]=2[F:33])[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 67968alpha-Bromo-o-fluorotolueneHCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 21226206Ethyl acetate hexane

Product 1

HCID 701493485(S)[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(o-fluorophenyl)methyl]dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-60 °C

Procedure

In analogy with Example 1h), 5.0 g (16.37 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one [Example 2b)] dissolved in 75 ml of THF are deprotonated, at -75° C., with 32.7 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated with 2.1 ml (18.0 mmol) of o-fluorobenzyl bromide (Fluka; Buchs/Switzerland) at -75° C. initially (heating to a maximum of -60° C. over a period of 60 min). Column chromatography (SiO2, hexane/ethyl acetate, 3:1) affords the title compound: TLC Rf (D)=0.61.

Sources & evidence

ORD record
ord-41b8553333cf4b72a5a3b66fb54cea97
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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