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

HRID 717884Notes

Reaction equation

HRID 717884 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-0f61f14fb45f4e73b083841bbb2f0c29
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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