4-Methylmorpholine → 1-Boc-4-(2-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)piperidine

HRID 2283945Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.CC(C)CC(Cl)=O.[Cl-].[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39](=[O:42])[CH2:40][NH3+:41])=[CH:35][C:34]=1[C:43]([F:46])([F:45])[F:44]>C1COCC1>[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39](=[O:42])[CH2:40][NH:41][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])=[CH:35][C:34]=1[C:43]([F:44])([F:45])[F:46]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (9611.92 mg; 41.92 mmol; 1.08 eq.) in THF 100 ml, added 4-methyl-morpholine (14.51 ml; 131.98 mmol; 3.40 eq.), The reaction mixture was cooled to −10° C., 3-methyl-butyryl chloride (5.03 ml; 38.82 mmol; 1.00 eq.) was add dropwise and maintaining the temperature below −5° C. after stirring for 30 mins at from −5° C. to 10° C., 2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethyl-ammonium chloride (10.00 g; 38.82 mmol; 1.00 eq.) was added at −5° C. and stirred the mixture for 20 mins and then RT for 1 h. Added brine, extracted with EA, washed with brine, dried and concentrated. The crude oil was treated with ether. The white solid was collected as the title compound (12 g, yield 71.5%).

Workup

temperaturemaintaining the temperature below −5° C.
additionwas added at −5° C.
waitRT for 1 h
extractionAdded brine, extracted with EA
washwashed with brine
customdried
concentrationconcentrated
additionThe crude oil was treated with ether

Sources & evidence

ORD record: ord-ca0a5c2d2eae40bfb4f34a7e278f05b6
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145392B2

Reaction notes

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