Sodium Hydroxide → [5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 1402149ノート

反応式

HRID 1402149 の反応式
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:3]=1.[OH-].[Na+].Cl[C:22]([O:24][CH2:25][C:26]([Cl:29])([Cl:28])[Cl:27])=[O:23]>CCOC(C)=O>[Cl:27][C:26]([Cl:29])([Cl:28])[CH2:25][O:24][C:22](=[O:23])[NH:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:3]=1

参加物

5

反応物 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 58532567(4-(5-Amino-3-tert-butyl-1H-pyrazol-1-yl)phenyl)methanol

生成物 1

HCID 89612285[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester収率 74%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of [4-(5-amino-3-tert-butyl-pyrazol-1-yl)-phenyl]-methanol (WO 2011/070368, which is incorporated herein by reference in its entirety; 3.05 g, 12.4 mmol) in aq. NaOH solution (1M, 31 mL, 31 mmol) and EtOAc (30 mL) at RT was added 2,2,2-trichloroethyl chloroformate (1.88 mL, 13.7 mmol) over 3 min (CARE: exotherm to 35° C.) and the mixture stirred at RT for 1 h. The aqueous layer was extracted with EtOAc (20 mL), then the combined organics washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave a pale orange solid. Recrystallisation from hot cyclohexane-EtOAc (3:1, 30 mL) and drying in vacuo gave the title compound as a flocculent off-white solid (3.87 g, 74%). LCMS (Method 3): Rt 4.00 min, m/z 420, 422 [MH+].

後処理

  1. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  2. washthe combined organics washed with brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto leave a pale orange solid
  7. customRecrystallisation from hot cyclohexane-EtOAc (3:1, 30 mL)
  8. customdrying in vacuo

出典と根拠

ORDレコード
ord-e3ebff96dc114c9b9903e75cde29c1a2
出典データセット
uspto-grants-2014_12
特許番号
US08907094B2

反応ノート

読み込み中…