Diisopropylethylamine → HCID 178459258, compound

HRID 2060058Notes

Reaction equation

HRID 2060058 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][C:11]1[C:12]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:13][C:14]([NH:18][CH:19]2[CH2:24][CH2:23][N:22]([C@H:25]3[CH2:30][CH2:29][C@H:28]([O:31][CH2:32][CH2:33][CH3:34])[CH2:27][CH2:26]3)[CH2:21][CH2:20]2)=[C:15]([OH:17])[CH:16]=1.[Cl:39][C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[ClH:39].[CH3:10][C:11]1[C:12]([S:35]([CH3:38])(=[O:36])=[O:37])=[CH:13][C:14]2[N:18]([CH:19]3[CH2:20][CH2:21][N:22]([C@H:25]4[CH2:26][CH2:27][C@H:28]([O:31][CH2:32][CH2:33][CH3:34])[CH2:29][CH2:30]4)[CH2:23][CH2:24]3)[C:40](=[O:42])[O:17][C:15]=2[CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178459259HCID 178459259, compound

Product 1

HCID 178459258HCID 178459258, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Hunig's base (0.01 mL, 0.06 mmol) was added to a solution of 5-methyl-4-(methylsulfonyl)-2-({1-[trans-4-(propyloxy)cyclohexyl]-4-piperidinyl}amino)phenol (D89, 14 mg, 0.03 mmol) in DCM (3 mL) at rt under Ar. The reaction was cooled to 0° C. and the triphosgene (5 mg, 0.02 mmol) was added. The mixture was stirred for 2 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 yellow oil, which 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 pale yellow oil. HCl (0.1 mL, 0.1 mmol, 1 M in Et2O) was added to a solution of the free base in DCM (0.5 mL) and the solvent was removed by rotary evaporation. The resulting solid was triturated with Et2O to give 6-methyl-5-(methylsulfonyl)-3-{1-[trans-4-(propyloxy)cyclohexyl]-4-piperidinyl}-1,3-benzoxazol-2(3H)-one hydrochloride (E31; 11 mg, 62%) as a cream 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 yellow oil, which
  7. customwas purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)

Sources & evidence

ORD record
ord-812011bafa8043599a3fbaab06373b1b
Source dataset
uspto-grants-2012_10
Patent number
US08278328B2

Reaction notes

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