Hydrogen chloride-ethyl acetate → methyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate

HRID 1026234Notes

Reaction equation

HRID 1026234 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:32]=[CH:31][C:9]3[N:10]=[C:11]([C:13]4[N:18]=[CH:17][C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26](C)(C)C)[CH3:22])=[CH:15][CH:14]=4)[O:12][C:8]=3[CH:7]=2)[CH2:3][CH2:2]1.Cl.C(OCC)(=O)C>C(OCC)(=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:32]=[CH:31][C:9]3[N:10]=[C:11]([C:13]4[N:18]=[CH:17][C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][CH3:26])[CH3:22])=[CH:15][CH:14]=4)[O:12][C:8]=3[CH:7]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86666262tert-butyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate

Product 1

HCID 67962162methyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamateYield 22.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate (84.6 mg), ethyl acetate (2 mL) and 4M hydrogen chloride/ethyl acetate (2 mL) was stirred at room temperature for 3 hr. The solvent was evaporated under reduced pressure, and the residue was mixed with triethylamine (0.5 mL), THF (2 mL) and methyl chloroformate (0.044 ml) at 0° C., and the obtained mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (17.5 mg).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was mixed with triethylamine (0.5 mL), THF (2 mL) and methyl chloroformate (0.044 ml) at 0° C.
  3. stirringthe obtained mixture was stirred at room temperature for 2 hr
  4. additionWater was added to the reaction mixture
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe combined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-5baa0cdf1db347ee9d40021567709be6
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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