4-Chlorobenzoyl chloride → tert-Butyl 2-(4-(3-(4-chlorophenyl)-3-oxopropanoyl)phenyl)morpholine-4-carboxylate

HRID 710237Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[Li].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:33][C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1>C1COCC1>[Cl:33][C:34]1[CH:42]=[CH:41][C:37]([C:38](=[O:39])[CH2:2][C:1]([C:4]2[CH:5]=[CH:6][C:7]([CH:10]3[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]3)=[CH:8][CH:9]=2)=[O:3])=[CH:36][CH:35]=1

Participants

Conditions

Temperature: -78 °C

Procedure

tert-Butyl 2-(4-acetylphenyl)morpholine-4-carboxylate (210 mg, 0.69 mmol) was dissolved in THF (3.5 ml). Lithium-bis-(trimethylsilyl)-amide solution (2.05 ml, 2.05 mmol, 1.0 M solution in THF) was added dropwise and the yellow reaction mixture was stirred at −78° C. for 1 hour. 4-Chlorobenzoyl chloride (120 mg, 0.69 mmol) was added and the reaction mixture was stirred for 90 min and was quenched by addition of 1M aqueous hydrochloric acid. Ethyl acetate was added and the organic layer was dried over MgSO4 and evaporated. The crude material was purified by flash chromatography (10 g silica gel, 10 to 50% ethyl acetate in heptane) to yield an off-white solid (215 mg, 70%). MS (ISP): 388.2 ([{35Cl}M-tBu+H]+), 390.3 ([{37Cl}M-tBu+H]+).

Workup

stirringthe reaction mixture was stirred for 90 min
customwas quenched by addition of 1M aqueous hydrochloric acid
additionEthyl acetate was added
dry with materialthe organic layer was dried over MgSO4
customevaporated
customThe crude material was purified by flash chromatography (10 g silica gel, 10 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-ae9c480ffaaa497b92be4b038445ee85
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181230B2

Reaction notes

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