4-(Methylthio)benzoyl chloride → Ethyl 2-(4-fluorophenyl)-3-(4-(methylthio)phenyl)-3-oxopropanoate

HRID 993315Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14][CH:13]=1.[CH3:24][S:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1>C1COCC1>[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH:18]([C:30]([C:29]2[CH:33]=[CH:34][C:26]([S:25][CH3:24])=[CH:27][CH:28]=2)=[O:31])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:16][CH:17]=1

Participants

Conditions

Temperature: -78 °C

Procedure

1 N Lithium bis(trimethylsilyl)amide (20 mL, 20 mmol) was added dropwise to a solution of ethyl (4-fluorophenyl)acetate prepared according to the method of Example 1A, (3.84 g, 20 mmol) in THF (20 mL) at −78° C. After 15 minutes the mixture was treated dropwise with a suspension of crude 4-(methylthio)benzoyl chloride (3.7 g, 20 mmol) in THF (50 mL), and the resulting mixture was stirred at −78° C. for 60 minutes. The reaction was quenched with saturated NH4Cl and extracted with ethyl acetate. The acetate layer was washed with water, brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was chromatographed (silica gel, 19:1 CH2Cl2-ethyl acetate) to provide the desired product (yield: 4.55 g; 69%). MS (DCI-NH3) m/z 333 (M+H)+, 350 (M+NH4)+; 1H NMR (300 MHz, CDCl3) δ1.25 (m, 3H), 2.50 (s, 3H), 4.20 (m, 2H), 5.53 (s, 1H), 7.03 (t, J=9 Hz, 2H), 7.22 (d, J=9 Hz, 2H), 7.38 (m, 2H), 7.85 (d, J=9 Hz, 2H).

Workup

customprepared
customThe reaction was quenched with saturated NH4Cl
extractionextracted with ethyl acetate
washThe acetate layer was washed with water, brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated in vacuo
customThe residue was chromatographed (silica gel, 19:1 CH2Cl2-ethyl acetate)

Sources & evidence

ORD record: ord-3d93479d1d0a4e2b97b948e6be3e2501
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06472416B1

Reaction notes

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