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Water → Methyl 5-[4-(difluoromethoxy)phenyl]-1-[(1-oxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylate

HRID 2091764
Notes
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Reaction equation

HRID 2091764 reaction equation
[F:1][CH:2]([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][NH:14][CH2:13][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:11]2)=[CH:6][CH:5]=1.C(N(CC)C(C)C)(C)C.[N:30]1([C:37](OC2C=CC([N+]([O-])=O)=CC=2)=[O:38])[CH2:35][CH2:34][S:33](=[O:36])[CH2:32][CH2:31]1.O>CN1CCCC1=O.C(OCC)(=O)C>[F:20][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:15][N:14]([C:37]([N:30]3[CH2:35][CH2:34][S:33](=[O:36])[CH2:32][CH2:31]3)=[O:38])[CH2:13][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:11]2)=[CH:8][CH:9]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 581165434-Nitrophenyl thiomorpholine-4-carboxylate 1-oxideHCID 58116573Methyl 5-[4-(difluoromethoxy)phenyl]piperidine-3-carboxylate

Product 1

HCID 58116576Methyl 5-[4-(difluoromethoxy)phenyl]-1-[(1-oxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylate

Reagents, catalysts & solvents

2
HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

2.2 g (7.7 mmol) of methyl 5-[4-(difluoromethoxy)phenyl]piperidine-3-carboxylate were dissolved in 14 ml of N-methylpyrrolidone, and admixed with 4.0 ml (3.0 g, 23.0 mmol) of N,N-diisopropylethylamine and 3.3 g (11.5 mmol) of 4-nitrophenyl thiomorpholine-4-carboxylate 1-oxide. The reaction mixture was converted in a microwave at 180° C. for seven minutes. Subsequently, water and ethyl acetate were added, and the aqueous phase was removed and extracted repeatedly with ethyl acetate. The combined organic extracts were washed with water and saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of preparative HPLC. Yield: 2.2 g (59% of theory)

Workup

  1. customthe aqueous phase was removed
  2. extractionextracted repeatedly with ethyl acetate
  3. washThe combined organic extracts were washed with water and saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-535bef791e304829a605b2cc82f1ab01
Source dataset
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08440657B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes