Diisopropylethylamine → HCID 178468168, compound

HRID 1969011Notes

Reaction equation

HRID 1969011 reaction equation
C(N(C(C)C)CC)(C)C.[CH2:10]([O:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:26]3[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=3[OH:33])[CH2:21][CH2:20]2)[CH2:15][CH2:14]1)[CH3:11].[Cl:34][C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[ClH:34].[CH2:10]([O:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([N:19]2[CH2:20][CH2:21][CH:22]([N:25]3[C:26]4[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=4[O:33][C:35]3=[O:37])[CH2:23][CH2:24]2)[CH2:15][CH2:14]1)[CH3:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 178468170HCID 178468170, compound

Product 1

HCID 178468168HCID 178468168, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Diisopropylethylamine (0.24 mL, 1.37 mmol) was added to a solution of 2-({1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}amino)-4-methylphenol (D29, 215 mg, 0.648 mmol) in dichloromethane (8 mL) at rt under argon. The reaction was cooled to 0° C. and the triphosgene (79 mg, 0.267 mmol) was added. The mixture was stirred for 30 min at 0° C., followed by a further 15 min at rt. The reaction was quenched with saturated aqueous NaHCO3 (10 mL) and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane (2×) and the combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a white solid. The residue was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane) to give the free base of the title compound as a white solid. The free base was dissolved in diethyl ether (1.5 mL) at 25° C. HCl (0.207 mL, 0.207 mmol, 1 M in diethyl ether) was then added and the reaction was stirred for 15 min. The solvent was removed by rotary evaporation to give 3-{1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}-5-methyl-1,3-benzoxazol-2(3H)-one hydrochloride (E10, 39.3 mg, 14% yield) as a white solid.

Workup

  1. waitfollowed by a further 15 min at rt
  2. customThe reaction was quenched with saturated aqueous NaHCO3 (10 mL)
  3. custompartitioned between dichloromethane and water
  4. extractionThe aqueous layer was extracted with dichloromethane (2×)
  5. dry with materialthe combined organics were dried (Na2SO4)
  6. concentrationconcentrated by rotary evaporation
  7. customto give a white solid
  8. customThe residue was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane)

Sources & evidence

ORD record
ord-25457ccb015b45f6846d9ed39b8ba6e0
Source dataset
uspto-grants-2013_04
Patent number
US08426443B2

Reaction notes

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