Trifluoroacetic acid → 1-((3-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid

HRID 1506331Notes

Reaction equation

HRID 1506331 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH2:29][N:30]3[CH2:33][CH:32]([C:34]([O:36]C(C)(C)C)=[O:35])[CH2:31]3)=[CH:23][CH:22]=5)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(C(F)(F)F)=O>ClCCl>[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH2:29][N:30]3[CH2:33][CH:32]([C:34]([OH:36])=[O:35])[CH2:31]3)=[CH:23][CH:22]=5)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67169968Tert-butyl 1-((3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylate

Product 1

HCID 532354811-((3-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 1-((3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylate (7C, 2.24 g, 4.06 mmol) in dichloromethane (4 mL) was added TFA (4 mL) slowly at room temperature. The reaction mixture was stirred at room temperature for 2 hr. The mixture was concentrated to remove dichloromethane and TFA (6 mL) was added. The mixture was stirred at room temperature till the starting material was observed to disappear. Dichloroethane (6 mL) was added and the mixture was concentrated under reduced pressure. The residue was mixed with water (10 mL), basified with 1 N aqueous NaOH to pH=8 and acidified with 1N aqueous HCl to pH=5. The mixture was sonicated for 30 min. The solid was filtered and washed with water (4×10 mL). The wet solid was mixed with methanol (40 mL), sonicated for 30 min, filtered, washed with methanol (3×10 mL), and dried to give 1-((3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid as a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. customto remove dichloromethane and TFA (6 mL)
  3. additionwas added
  4. stirringThe mixture was stirred at room temperature till the starting material
  5. additionDichloroethane (6 mL) was added
  6. concentrationthe mixture was concentrated under reduced pressure
  7. additionThe residue was mixed with water (10 mL)
  8. customThe mixture was sonicated for 30 min
  9. filtrationThe solid was filtered
  10. washwashed with water (4×10 mL)
  11. additionThe wet solid was mixed with methanol (40 mL)
  12. customsonicated for 30 min
  13. filtrationfiltered
  14. washwashed with methanol (3×10 mL)
  15. customdried

Sources & evidence

ORD record
ord-c07e994c5d1f4e8fb34afdcf888b7363
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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