N-methyl-2-pyrrolidone → Methyl 5-[3-fluoro-4-(trifluoromethyl)phenyl]-1-(thiomorpholin-4-ylcarbonyl)piperidine-3-carboxylate

HRID 661253Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:12]2[CH2:17][N:16]([C:18]([O:20]C3C=CC([N+]([O-])=O)=CC=3)=O)[CH2:15][CH:14]([C:30]([O:32][CH3:33])=[O:31])[CH2:13]2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[NH:34]1[CH2:39][CH2:38][S:37][CH2:36][CH2:35]1.C(N(CC)C(C)C)(C)C.CN1CCCC1=O>C(OCC)(=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:12]2[CH2:17][N:16]([C:18]([N:34]3[CH2:39][CH2:38][S:37][CH2:36][CH2:35]3)=[O:20])[CH2:15][CH:14]([C:30]([O:32][CH3:33])=[O:31])[CH2:13]2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:9])[F:10]

Participants

Conditions

Temperature: 150 °C

Procedure

651 mg (1.38 mmol) of the compound from Example 83A, 0.99 g (9.69 mmol) of thiomorpholine and 0.84 ml (0.63 g, 4.84 mmol) of N,N-diisopropylethylamine were added to 9 ml of 1-methyl-2-pyrrolidone and heated in a single-mode microwave (Emrys Optimizer) at 150° C. for 1 h. For workup, the reaction solution was admixed with water. After addition of ethyl acetate and phase separation, the organic phase was washed with aqueous 1 N hydrochloric acid solution, dried (magnesium sulphate), filtered and concentrated under reduced pressure. This gave 550 mg of crude product in 80% purity (LC-MS), which was reacted without any further purification steps.

Workup

washthe organic phase was washed with aqueous 1 N hydrochloric acid solution
dry with materialdried (magnesium sulphate)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThis gave 550 mg of crude product in 80% purity (LC-MS), which was reacted without any further purification steps

Sources & evidence

ORD record: ord-e029c5cc0096432492f92639636d71ae
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08084469B2

Reaction notes

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