Sodium borohydride → Tert-butyl 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

HRID 717884노트

반응식

HRID 717884 반응식
[BH4-].[Na+].[CH:3]([C:5]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[N:8]=[C:7]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:6]=1)=[O:4]>C(O)(C)C>[OH:4][CH2:3][C:5]1[N:10]=[C:9]([C:11]([F:13])([F:12])[F:14])[N:8]=[C:7]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:6]=1

참가 물질

4

반응물 2

HCID 4311764Sodium borohydrideHCID 86706863Tert-butyl 4-{[6-formyl-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

생성물 1

HCID 86706864Tert-butyl 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

Sodium tetrahydroborate (73 mg, 1.9 mmol) was added to a solution of tert-butyl 4-{[6-formyl-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (0.90 g, 1.9 mmol, from Step 3) in Isopropyl alcohol (15 mL) at 0° C. After stirring at this temperature for 1.5 hours, the reaction was quenched by the addition of saturated ammonium chloride. The mixture was further diluted with water and extracted with EtOAc. The organic extract was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes afforded product as a white solid (0.58 g, 80% over the two steps). 1H NMR (400 MHz, CDCl3) δ 6.50 (s, 1H), 4.66 (d, J=5.1 Hz, 2H), 4.30-3.89 (m, 2H), 2.95 (t, J=12.0 Hz, 2H), 2.73 (t, J=5.2 Hz, 1H), 2.22-1.88 (m, 2H), 1.53-1.33 (m, 11H). 19F NMR (376 MHz, CDCl3) δ −71.74 (s). LCMS (M+H)+: 377.1.

후처리

  1. customthe reaction was quenched by the addition of saturated ammonium chloride
  2. additionThe mixture was further diluted with water
  3. extractionextracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes afforded product as a white solid (0.58 g, 80% over the two steps)

출처 및 근거

ORD 기록
ord-0f61f14fb45f4e73b083841bbb2f0c29
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193733B2

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