Methanol → HCID 70855386, compound

HRID 591050Notes

Reaction equation

HRID 591050 reaction equation
[C:1](Cl)(=[O:3])C.[O:5]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[N:19]([CH3:20])[N:18]=[C:17]([CH3:21])[C:16]=3[CH:22]([O:25][Si](C)(C)C)[C:23]#N)=[CH:14][C:9]=2[CH2:8][CH2:7][CH2:6]1.C[OH:31]>>[O:5]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[N:19]([CH3:20])[N:18]=[C:17]([CH3:21])[C:16]=3[CH:22]([OH:25])[C:23]([O:3][CH3:1])=[O:31])=[CH:14][C:9]=2[CH2:8][CH2:7][CH2:6]1

Participants

4

Reactant 3

HCID 887MethanolHCID 6367Acetyl chlorideHCID 70818853HCID 70818853, compound

Product 1

HCID 70855386HCID 70855386, compoundYield 55%

Procedure

Acetyl chloride (0.35 mL, 4.96 mmol) was added to anhydrous methanol (3 mL) at 0° C. under nitrogen atmosphere. The mixture was stirred for 20 minutes before adding 2-[5-(3,4-dihydro-2H-1-benzopyran-6-yl)-1,3-dimethyl-1H-pyrazol-4-yl]-2-[(trimethylsilyl)oxy]acetonitrile (27b) (147 mg, 0.41 mmol). The mixture was stirred at room temperature for 1 hour then at 50-60° C. for 5 hours. The solution was concentrated in vacuo. A saturated solution of sodium hydrogencarbonate (10 mL) was added to the residue. The aqueous layer was extracted with ethyl acetate (2×10 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 40/60) to provide the desired hydroxyl-ester (27c) (72 mg, 0.227 mmol, 55%) as a colorless oil.

Workup

  1. stirringThe mixture was stirred at room temperature for 1 hour
  2. waitat 50-60° C. for 5 hours
  3. concentrationThe solution was concentrated in vacuo
  4. additionA saturated solution of sodium hydrogencarbonate (10 mL) was added to the residue
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  6. washThe organic layer was washed with brine (10 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 40/60)

Sources & evidence

ORD record
ord-4066fd21751d4f9b9a1569c00cc2bfaf
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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