Hydrochloric Acid → Tert-butyl 2-(3-cyano-4-fluorophenyl)propanoate

HRID 453552Notes

Reaction equation

[CH:1](NC(C)C)(C)C.C([Li])CCC.[C:13]([C:15]1[CH:16]=[C:17]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:18]=[CH:19][C:20]=1[F:21])#[N:14].CI.Cl>C1COCC1>[C:13]([C:15]1[CH:16]=[C:17]([CH:22]([CH3:1])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:18]=[CH:19][C:20]=1[F:21])#[N:14]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of diisopropylamine in 2 ml of THF at −78° C. was added n-butyl lithium (0.61 ml). The reaction was stirred for 30 minutes after which time a solution of tert-butyl 2-(3-cyano-4-fluorophenyl)acetate (0.300 g) in THF (2 ml) was added dropwise over 20 minutes at −78° C. The reaction was warmed to 0° C. and then transferred a flask containing 2 ml THF and MeI (0.080 ml). The reaction was acidified with 2M HCl and extracted with ethyl acetate. The combined organics were then washed with brine and dried over MgSO4. The concentrated product was purified by silica gel chromatography using a solvent system of 5% to 50% ethyl acetate/hexanes to provide tert-butyl 2-(3-cyano-4-fluorophenyl)propanoate (0.140 g).

Workup

additionwas added dropwise over 20 minutes at −78° C
extractionextracted with ethyl acetate
washThe combined organics were then washed with brine
dry with materialdried over MgSO4
customThe concentrated product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-0ab84e105de94641957e4c8c79a6f7e0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492437B2

Reaction notes

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