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

HRID 391485노트

반응식

HRID 391485 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매3회

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-bc3e67ca5bc342ebb5655eb3ac39df03
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383821B2

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