Diisopropylethylamine → HCID 67321823, compound

HRID 1968952Notes

Reaction equation

HRID 1968952 reaction equation
[CH3:1][CH2:2]N(C(C)C)C(C)C.[C:10]([C:12]1[CH:13]=[CH:14][C:15]([OH:32])=[C:16]([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)[CH:17]=1)#[N:11].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[C:10]([C:12]1[CH:13]=[CH:14][C:15]2[O:32][C:1](=[CH2:2])[N:18]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:21][CH2:20]3)[C:16]=2[CH:17]=1)#[N:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 59444107HCID 59444107, compound

Product 1

HCID 67321823HCID 67321823, compoundYield 116%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Hünig's base (1 mL, 5.73 mmol) was added to a solution of 1,1-dimethylethyl 4-[(5-cyano-2-hydroxyphenyl)amino]-1-piperidinecarboxylate (D32, 977 mg, 3.08 mmol) in dichloromethane (20 mL) at rt under argon. The reaction was cooled to 0° C. and triphosgene (373 mg, 1.26 mmol) was added. The reaction was then stirred for 30 min at 0° C. and quenched with saturated aqueous NaHCO3 (20 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 a yellow oil. The crude residue was purified via chromatography (silica, Biotage 40+S column, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane) to give 1,1-dimethylethyl 4-(5-cyano-2-methylidene-1,3-benzoxazol-3(2H)-yl)-1-piperidinecarboxylate (D33, 1.22 g, 92% yield, 82% purity by LC-MS) as a yellow oil.

Workup

  1. customquenched with saturated aqueous NaHCO3 (20 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 a yellow oil
  7. customThe crude residue was purified via chromatography (silica, Biotage 40+S column, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane)

Sources & evidence

ORD record
ord-dac2b3d3cba94ee8b2f82b8b1dfdb074
Source dataset
uspto-grants-2013_04
Patent number
US08426443B2

Reaction notes

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