Diisopropylethylamine → HCID 58287304, compound

HRID 1798917Notes

Reaction equation

HRID 1798917 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([NH:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[C:13]([OH:32])[CH:12]=1.Cl[C:34](Cl)([O:36]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[F:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]2[N:18]([CH:19]3[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:23][CH2:24]3)[C:34](=[O:36])[O:32][C:13]=2[CH:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 58287316HCID 58287316, compound

Product 1

HCID 58287304HCID 58287304, compoundYield 276.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Hünig's base (0.5 mL, 2.86 mmol) was added to a solution of 1,1-dimethylethyl 4-[(4-fluoro-2-hydroxy-5-methylphenyl)amino]-1-piperidinecarboxylate (D1, 593 mg, 1.34 mmol) in dichloromethane (10 mL) at rt under argon. The reaction was cooled to 0° C. and the triphosgene (167 mg, 0.564 mmol) was added. The reaction was then stirred for 1.5 h at 0° C. and quenched with saturated aqueous NaHCO3 (10 mL) before being 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 an orange oil. The residue was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane) to give 1,1-dimethylethyl 4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidine carboxylate (D2, 546 mg, 73% purity, 85% yield) as an orange oil.

Workup

  1. customquenched with saturated aqueous NaHCO3 (10 mL)
  2. custombefore being partitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane (2×)
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. concentrationconcentrated by rotary evaporation
  6. customto give an orange oil
  7. customThe residue was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane)

Sources & evidence

ORD record
ord-2e9666c1ccf249e68594720768cb218e
Source dataset
uspto-grants-2013_01
Patent number
US08344000B2

Reaction notes

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