Diisopropylethylamine → [5-tert-Butyl-2-(3-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 75603Notes

Reaction equation

HRID 75603 reaction equation
[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](Cl)=[O:6].[C:10]([C:14]1[CH:15]=[C:16]([NH2:36])[N:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])[CH:20]=2)[N:18]=1)([CH3:13])([CH3:12])[CH3:11].CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](=[O:6])[NH:36][C:16]1[N:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][Si:26]([CH:27]([CH3:29])[CH3:28])([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:31])[CH3:32])[CH:20]=2)[N:18]=[C:14]([C:10]([CH3:11])([CH3:13])[CH3:12])[CH:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 866867005-tert-Butyl-2-(3-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-ylamine

Product 1

HCID 86686701[5-tert-Butyl-2-(3-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterYield 99.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,2,2-Trichloroethylchloroformate (1.09 mL, 7.92 mmol) was added to a solution of Intermediate 22a (1.53 g, 3.96 mmol) and DIPEA (2.75 mL, 15.8 mmol) in THF (40 mL) at 0° C. The reaction was stirred at RT for 3 h then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (2.22 g, 99%). LCMS (Method 4): Rt 5.55 min, m/z 560, 562 [MH+].

Workup

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was then extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-ab61fce7ccdd40259c404d01f8c7ff53
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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