Methanol → HCID 71257347, compound

HRID 2200811Notes

Reaction equation

HRID 2200811 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([C:22]([CH3:28])([CH3:27])[C:23](OC)=[O:24])[CH:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.O1CCCC1.[BH4-].[Na+].CO>>[O:4]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[N:15]=[C:14]([C:22]([CH3:28])([CH3:27])[CH2:23][OH:24])[CH:13]=3)[CH2:7][CH2:6]2)[O:1][CH2:2][CH2:3]1

Participants

5

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 71257262HCID 71257262, compound

Product 1

HCID 71257347HCID 71257347, compoundYield 82.7%

Procedure

Methyl 2-[6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]-2-methylpropanoate (0.299 g, 0.739 mmol) was dissolved in tetrahydrofuran (6 mL, 80 mmol). Sodium tetrahydroborate was then added (70. mg, 1.8 mmol), followed by methanol (450 μL, 11 mmol) in portions. The reaction mixture was stirred 30 min, at which point LCMS showed 50% conversion. After 2 h, LCMS showed no remaining ester, and showed the product (M+H 377), and several over-reduction by-products. The reaction was quenched with water, the solvent removed by rotary evaporation. Aqueous bicarbonate was added, and then EtOAc was added. The mixture was then stirred 0.5 h. The EtOAc layer was shaken with brine, dried (Na2SO4), and the solvent removed by rotary evaporation. The product was purified by automatic silica gel chromatography on a 40 g silica gel column, using solvent A=hexane; solvent B=2% iPA/EtOAc; flow 40 mL/min; A, 2 min; gradient to 30% B in 35 min; detector set at 254 nm; retention time, 26 min. The solvent was removed by rotary evaporation to yield 230 mg of a colorless viscous oil.

Workup

  1. waitAfter 2 h
  2. customThe reaction was quenched with water
  3. customthe solvent removed by rotary evaporation
  4. additionAqueous bicarbonate was added
  5. additionEtOAc was added
  6. stirringThe mixture was then stirred 0.5 h
  7. stirringThe EtOAc layer was shaken with brine
  8. dry with materialdried (Na2SO4)
  9. customthe solvent removed by rotary evaporation
  10. customThe product was purified by automatic silica gel chromatography on a 40 g silica gel column
  11. custom2 min
  12. waitgradient to 30% B in 35 min
  13. customretention time, 26 min
  14. customThe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-60118b2f0c9a4dbeb419b740934e4265
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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