Sodium triacetoxyborohydride → 4-((3-Bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2,4-difluorophenyl)-1-methylpiperidine

HRID 391485ノート

反応式

HRID 391485 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=2[F:28])[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([C:32]([F:34])([F:35])[F:33])[CH:31]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=2[F:28])[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]1

参加物

4

反応物 2

HCID 5049666Sodium triacetoxyborohydrideHCID 58993590tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2,4-difluorophenyl)piperidine-1-carboxylate

生成物 1

HCID 589935934-((3-Bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2,4-difluorophenyl)-1-methylpiperidine

試薬・触媒・溶媒 1

HCID 887Methanol溶媒3 回

実験手順

tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2,4-difluorophenyl)piperidine-1-carboxylate (200 mg, 0.35 mmol) was dissolved in methanol (5 mL). Hydrochloric acid (gas) was bubbled through for 20 seconds, then removed. The reaction was allowed to stir for 20 min and the solvent evaporated. The resulting solid was dissolved in dichloromethane (2 mL) and treated with formaldehyde (37 wt. % solution in water, 1.5 mL) at 0° C. After 20 min the reaction was treated with sodium triacetoxyborohydride (297 mg, 1.4 mmol). The reaction was stirred at 0° C. for 30 min and at room temperature for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvents were evaporated to afford 142 mg (85%). Mass Spec: 478.07 (MH)+. LC tr=1.885 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=2 min, Flow rate=4 mL/min).

後処理

  1. customHydrochloric acid (gas) was bubbled through for 20 seconds
  2. customremoved
  3. customthe solvent evaporated
  4. dissolutionThe resulting solid was dissolved in dichloromethane (2 mL)
  5. additiontreated with formaldehyde (37 wt. % solution in water, 1.5 mL) at 0° C
  6. stirringThe reaction was stirred at 0° C. for 30 min and at room temperature for 1 h
  7. customThe solvent was removed in vacuo
  8. washAfter washing the column with several volumes of methanol
  9. washthe product was eluted
  10. washby washing the column with 2 M ammonia in methanol
  11. customThe solvents were evaporated
  12. customto afford 142 mg (85%)

出典と根拠

ORDレコード
ord-bc3e67ca5bc342ebb5655eb3ac39df03
出典データセット
uspto-grants-2013_02
特許番号
US08383821B2

反応ノート

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