Hydrochloric Acid → HCID 42633440, compound

HRID 2388240Notes

Reaction equation

HRID 2388240 reaction equation
[OH:1][C:2]1[C:3]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[C:5]([C:13]([F:16])([F:15])[F:14])=[N:6][C:7]=1[C:8](OCC)=[O:9].[NH2:26][CH2:27][C:28]([OH:30])=[O:29].[O-]CC.[Na+].Cl>CCOC(C)=O.O.CN(C=O)C>[OH:1][C:2]1[C:3]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[C:5]([C:13]([F:14])([F:15])[F:16])=[N:6][C:7]=1[C:8]([NH:26][CH2:27][C:28]([OH:30])=[O:29])=[O:9]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 750GlycineHCID 2723922Sodium ethoxideHCID 67531028HCID 67531028, compound

Product 1

HCID 42633440HCID 42633440, compoundYield 57.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 7-hydroxy-3-phenyl-4-(trifluoromethyl)isoxazolo[4,5-c]pyridine-6-carboxylate (58 mg, 0.17 mmol), glycine (247 mg, 3.30 mmol), and sodium ethoxide (168 mg, 2.47 mmol) were added to 6 mL of DMF and the mixture was refluxed for 2 h. After the mixture cooled to room temperature, water (50 mL) and EtOAc (50 mL) were added. The mixture was stirred vigorously and 4M hydrochloric acid was added until pH was 3. The aqueous layer was extracted with additional EtOAc and the combined organic layer was dried over MgSO4 and concentrated. The residue was taken up in saturated sodium bicarbonate solution (20 mL) and washed with hexanes and EtOAc. The aqueous layer was acidified to pH 3 with 4M hydrochloric acid and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give a crude solid, which was purified by flash chromatography (0-100% EtOAc/hexanes+2% acetic acid) to give 37 mg of the title compound. MS: (−) m/z 380.19 (M−1).

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. dry with materialthe combined organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. washwashed with hexanes and EtOAc
  6. extractionextracted with EtOAc
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated
  9. customto give a crude solid, which
  10. customwas purified by flash chromatography (0-100% EtOAc/hexanes+2% acetic acid)

Sources & evidence

ORD record
ord-67e8e306990549d4a904eed69a54a2f7
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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