4-(Trifluoromethyl)piperidine hydrochloride → methyl 1-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate

HRID 2421888Notes

Reaction equation

HRID 2421888 reaction equation
Cl[S:2]([N:5]1[CH2:10][CH2:9][O:8][C:7]2[N:11]=[CH:12][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][C:6]1=2)(=[O:4])=[O:3].Cl.[F:20][C:21]([F:29])([F:28])[CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>C(Cl)Cl>[F:20][C:21]([F:29])([F:28])[CH:22]1[CH2:27][CH2:26][N:25]([S:2]([N:5]2[CH2:10][CH2:9][O:8][C:7]3[N:11]=[CH:12][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][C:6]2=3)(=[O:4])=[O:3])[CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 57896693methyl 1-(chlorosulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate

Product 1

HCID 57896759methyl 1-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylateYield 80.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of methyl 1-(chlorosulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (250 mg, 0.854 mmol) in DCM (10 mL) at −10° C. was added TEA (0.595 mL, 4.27 mmol) and 4-(trifluoromethyl)piperidine hydrochloride (324 mg, 1.708 mmol). The reaction was allowed to stir for 3 h at −10° C. and slowly warmed to room temperature over 2 h. The reaction was allowed to stir at room temperature for 16 h. The reaction mixture was diluted with DCM (10 mL) and washed with H2O (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was purified by flash column chromatography using a gradient elution of DCM with 0-25% acetonitrile to provide methyl 1-(4-(trifluoromethyl)piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (280 mg, 0.684 mmol, 80% yield) as a white solid. LCMS (+ESI) m/z=410.1 [M+H]+.

Workup

  1. temperatureslowly warmed to room temperature over 2 h
  2. stirringto stir at room temperature for 16 h
  3. washwashed with H2O (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting solid was purified by flash column chromatography
  7. washa gradient elution of DCM with 0-25% acetonitrile

Sources & evidence

ORD record
ord-ea93b97c814840699187d645700db978
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

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