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

HRID 717884ノート

反応式

HRID 717884 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-0f61f14fb45f4e73b083841bbb2f0c29
出典データセット
uspto-grants-2015_11
特許番号
US09193733B2

反応ノート

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