2-(Bromomethyl)benzonitrile → 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-(o-cyanophenylmethyl)-dihydrofuran-2-(3H)-one

HRID 263766Notes

Reaction equation

HRID 263766 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+].Br[CH2:34][C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[C:37]#[N:38].CCCCCC.C(OCC)(=O)C>C1COCC1.CCCCCC>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:34][C:35]2[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=2[C:37]#[N:38])[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

7

Reactant 4

HCID 895992-(Bromomethyl)benzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 21226206Ethyl acetate hexane

Product 1

HCID 677188185(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-(o-cyanophenylmethyl)-dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Analogously to Example 21 D) 1)c), 2.0 g (6.55 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-dihydrofuran-2-(3H)-one [Example 21 D) 1)b)] dissolved in 40 ml of THF are deprotonated with 13.1 ml of lithium bis(trimethylsilyl)amide 1M in THF and alkylated (75 min) with 1.4 g (7.2 mmol) of 2-bromomethylbenzonitrile (Fluka; Buchs/Switzerland). Column chromatography (SiO2, hexane/ethyl acetate 2:1) and stirring in hexane yields the pure title compound: TLC Rf (D)=0.45; tRet (I)=16.2 min.

Workup

  1. custom(75 min)

Sources & evidence

ORD record
ord-f0c70276eb3f40aeb7288bd9c3579d10
Source dataset
uspto-grants-1997_07
Patent number
US05643878

Reaction notes

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