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

HRID 1026349Notes

Reaction equation

HRID 1026349 reaction equation
[F:1][C:2]1([F:36])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:35]=[CH:34][C:11]3[N:12]=[C:13]([C:15]4[N:20]=[CH:19][C:18]([O:21][CH2:22][C@@H:23]([NH:25]C(=O)OC(C)(C)C)[CH3:24])=[CH:17][C:16]=4[F:33])[O:14][C:10]=3[CH:9]=2)[CH2:3]1.Cl.[C:38](OCC)(=[O:40])[CH3:39]>C(OCC)(=O)C>[F:36][C:2]1([F:1])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:35]=[CH:34][C:11]3[N:12]=[C:13]([C:15]4[N:20]=[CH:19][C:18]([O:21][CH2:22][C@@H:23]([NH:25][C:38](=[O:40])[CH3:39])[CH3:24])=[CH:17][C:16]=4[F:33])[O:14][C:10]=3[CH:9]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86666323tert-butyl {(1S)-2-[(6-{6-[(3,3-difluorocyclobutyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate

Product 1

HCID 67778439N-{(1S)-2-[(6-{6-[(3,3-difluorocyclobutyl)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-[(3,3-difluorocyclobutyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate (390 mg), 4 M hydrogen chloride/ethyl acetate (3 mL), and ethyl acetate (3 mL) was stirred at room temperature for 4 hr. The mixture was concentrated under reduced pressure. The residue was mixed with pyridine (3 mL) and acetic anhydride (1 mL). The mixture was stirred at room temperature for 3 days. 1 M hydrochloric acid was added, and the mixture was extracted with ethyl is 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/methanol) and recrystallization (ethyl acetate) to give the title compound (218 mg) as white crystals.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionThe residue was mixed with pyridine (3 mL) and acetic anhydride (1 mL)
  3. stirringThe mixture was stirred at room temperature for 3 days
  4. addition1 M hydrochloric acid was added
  5. extractionthe mixture was extracted with ethyl
  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/methanol) and recrystallization (ethyl acetate)

Sources & evidence

ORD record
ord-34f7a937fdd8415a8a2400baede4621d
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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