4-(Bromomethyl)benzonitrile → 3-(4-Cyanophenyl)-2-(pyrrolidin-2-yl)-propionic acid methyl ester

HRID 901325Notes

Reaction equation

HRID 901325 reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH2:4][C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1C(OC(C)(C)C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1>>[CH3:1][O:2][C:3](=[O:17])[CH:4]([CH:5]1[CH2:9][CH2:8][CH2:7][NH:6]1)[CH2:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1

Participants

4

Reactant 3

HCID 869964-(Bromomethyl)benzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 12990562tert-butyl (2R)-2-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate

Product 1

HCID 692559163-(4-Cyanophenyl)-2-(pyrrolidin-2-yl)-propionic acid methyl ester

Procedure

(R)-1-(tert-Butyloxycarbonyl)pyrrolidin-2-yl-acetic acid methyl ester (0.5 g, 2.06 mmol) is treated with lithium bis(trimethylsilyl)amide and 4-bromomethylbenzonitrile (1.0 g, 5.14 mmol) as described in EXAMPLE 1B to give 3-(4-cyanophenyl)-2-(pyrrolidin-2-yl)-propionic acid methyl ester as a mixture of stereoisomers. This material is coupled with biphenyl-4-carboxylic acid to give 2-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-3-(4-cyanophenyl)-propionic acid methyl ester (0.5 g, 1.1 mmol). This material is converted to the title compound (0.47 g, 0.83 mmol) by the procedure described in EXAMPLE 1C. 1H NMR (DMSO-d6, 300 MHz) □ 9.35-9.11(m,4H), 7.78-7.32 (m, 13H), 4.52, 4.36(two m, 1H), 3.58, 3.51 (two s, 3H), 3.50-3.25(m,3H), 3.14-2.95(m, 1H), 2.95-2.80(m, 1H), 2.20-1.55(m, 4H). MS m/z: [M+H]+=456

Sources & evidence

ORD record
ord-97586c157441411c8ae2faab6a9ad497
Source dataset
uspto-grants-2008_04
Patent number
US07361663B2

Reaction notes

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