Hydrogen chloride-ethyl acetate → N-{(1S)-2-[(6-{6-[(2,2-difluorocyclopropyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}acetamide

HRID 1026329Notes

Reaction equation

HRID 1026329 reaction equation
[F:1][C:2]1([F:35])[CH2:4][CH:3]1[CH2:5][O:6][C:7]1[CH:34]=[CH:33][C:10]2[N:11]=[C:12]([C:14]3[N:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=[O:31])OC(C)(C)C)[CH3:23])=[CH:16][C:15]=3[F:32])[O:13][C:9]=2[CH:8]=1.Cl.[C:37](OCC)(=O)C>C(OCC)(=O)C>[F:35][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][O:6][C:7]1[CH:34]=[CH:33][C:10]2[N:11]=[C:12]([C:14]3[N:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=[O:31])[CH3:37])[CH3:23])=[CH:16][C:15]=3[F:32])[O:13][C:9]=2[CH:8]=1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86666313tert-butyl {(1S)-2-[(6-{6-[(2,2-difluorocyclopropyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate

Product 1

HCID 67777764N-{(1S)-2-[(6-{6-[(2,2-difluorocyclopropyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}acetamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl {(1S)-2-[(6-{6-[(2,2-difluorocyclopropyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate (690 mg), 4 M hydrogen chloride/ethyl acetate (10 mL), and ethyl acetate (10 mL) was stirred at room temperature overnight. The mixture was concentrated under reduced pressure. The residue was mixed with pyridine (10 mL) and acetic anhydride (5 mL). The mixture was stirred at room temperature overnight. 1 M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) and recrystallization (ethyl acetate) to give the title compound (496 mg) as white crystals.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionThe residue was mixed with pyridine (10 mL) and acetic anhydride (5 mL)
  3. stirringThe mixture was stirred at room temperature overnight
  4. addition1 M hydrochloric acid was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate) and recrystallization (ethyl acetate)

Sources & evidence

ORD record
ord-70ebd38f02604f1c8e2d2b99645a89df
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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