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

HRID 220033Notes

Reaction equation

HRID 220033 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:38](OC2C=CC([N+]([O-])=O)=CC=2)=[O:39])[CH2:35][CH2:34][S:33](=[O:37])(=[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:38]([N:30]3[CH2:35][CH2:34][S:33](=[O:37])(=[O:36])[CH2:32][CH2:31]3)=[O:39])[CH2:13][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:11]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 581165414-Nitrophenyl thiomorpholine-4-carboxylate 1,1-dioxideHCID 58116573Methyl 5-[4-(difluoromethoxy)phenyl]piperidine-3-carboxylate

Product 1

HCID 58116465Methyl 5-[4-(difluoromethoxy)phenyl]-1-[(1,1-dioxidothiomorpholin-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 3.5 g (11.5 mmol) of 4-nitrophenyl thiomorpholine-4-carboxylate 1,1-dioxide. 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 taken up in diethyl ether and filtered, and the filtrate was purified by means of preparative HPLC. Yield: 2.0 g (51% 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. filtrationfiltered
  8. customthe filtrate was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-a94405b29a9d4c23b33d404d011919cb
Source dataset
uspto-grants-2012_06
Patent number
US08202862B2

Reaction notes

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