Diisopropylethylamine → 3-[1-(4-Methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-benzoxazol-2(3H)-one hydrochloride

HRID 1798934Notes

Reaction equation

HRID 1798934 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][C:11]1([N:17]2[CH2:22][CH2:21][CH:20]([NH:23][C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=3[OH:34])[CH2:19][CH2:18]2)[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[Cl:35][C:36](Cl)([O:38]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[ClH:35].[CH3:10][C:11]1([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[C:24]4[CH:29]=[C:28]([C:30]([F:32])([F:33])[F:31])[CH:27]=[CH:26][C:25]=4[O:34][C:36]3=[O:38])[CH2:19][CH2:18]2)[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 582873072-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol

Product 1

HCID 672209253-[1-(4-Methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-benzoxazol-2(3H)-one hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DIPEA (0.1 mL, 0.57 mmol) was added to a solution of 2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol (D14, 89 mg, 0.25 mmol) in DCM (5 mL) at rt under Ar. The reaction was cooled to 0° C. and the triphosgene (31 mg, 0.10 mmol) was added. The mixture was stirred for 3 h at 0° C. The reaction was quenched with sat. NaHCO3 (5 mL) and partitioned between DCM and H2O. The aqueous layer was extracted with DCM (2×) and the combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a pale yellow solid. The residue was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give the free base of the title compound as a colourless oil. HCl (0.5 mL, 0.5 mmol, 1 M in Et2O) was added to a solution of the free base in DCM (5 mL) and the reaction stirred for 30 min. The solvent was removed by rotary evaporation and the resulting solid triturated with Et2O to give 3-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-benzoxazol-2(3H)-one hydrochloride (E3, 81 mg, 73%) as a white solid.

Workup

  1. customThe reaction was quenched with sat. NaHCO3 (5 mL)
  2. custompartitioned between DCM and H2O
  3. extractionThe aqueous layer was extracted with DCM (2×)
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. concentrationconcentrated by rotary evaporation
  6. customto give a pale yellow solid
  7. customThe residue was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)

Sources & evidence

ORD record
ord-945c90a17208480f8c4999d5fce3dbdb
Source dataset
uspto-grants-2013_01
Patent number
US08344000B2

Reaction notes

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