Methanol → HCID 86666514, compound

HRID 1426366Notes

Reaction equation

HRID 1426366 reaction equation
[BH4-].[Na+].C[O:4][C:5](=O)[CH2:6][C:7]1[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([O:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:8]=1.CO>O1CCCC1>[OH:4][CH2:5][CH2:6][C:7]1[N:12]=[C:11]([C:13]([F:15])([F:16])[F:14])[N:10]=[C:9]([O:17][CH:18]2[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]2)[CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 69673273HCID 69673273, compound

Product 1

HCID 86666514HCID 86666514, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium tetrahydroborate (32 mg, 0.83 mmol) was added to a solution of tert-butyl 4-{[6-(2-methoxy-2-oxoethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate (125 mg, 0.209 mmol, from Step 2) in tetrahydrofuran (2.0 mL). Methanol (0.21 mL) was added in portions. After stirring for 2 hours, the mixture was quenched by the addition of saturated ammonium chloride solution. The reaction was diluted with additional water, and the product was extracted with EtOAc. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on a 12 g silica gel column, eluting with a gradient from 0-30% EtOAc in hexanes afforded product (26 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 6.74 (s, 1H), 5.35 (tt, J=7.8, 3.7 Hz, 1H), 4.07-3.96 (m, 2H), 3.81-3.61 (m, 2H), 3.31 (ddd, J=13.5, 8.4, 3.7 Hz, 2H), 2.99 (t, J=5.4 Hz, 2H), 2.03-1.92 (m, 2H), 1.79-1.68 (m, 2H), 1.47 (s, 9H); 19F NMR (376 MHz, CDCl3) δ-71.37 (s); LCMS (M+Na)+: 414.0.

Workup

  1. customthe mixture was quenched by the addition of saturated ammonium chloride solution
  2. additionThe reaction was diluted with additional water
  3. extractionthe product was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washFlash chromatography on a 12 g silica gel column, eluting with a gradient from 0-30% EtOAc in hexanes afforded product (26 mg, 32%)

Sources & evidence

ORD record
ord-100c83df6a8547cd98d343ba621bb8c1
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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