Hydrochloric Acid → 3-Methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl) isoxazole-5-carboxamido)butanoic acid

HRID 75831Notes

Reaction equation

HRID 75831 reaction equation
[CH3:1][CH:2]([CH3:36])[CH:3]([NH:8][C:9]([C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)=[O:24])=[CH:18][CH:17]=2)[CH:12]=1)=[O:10])[C:4]([O:6]C)=[O:5].O.[OH-].[Li+].Cl>C1COCC1>[CH3:1][CH:2]([CH3:36])[CH:3]([NH:8][C:9]([C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:23]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([C:32]([F:34])([F:33])[F:35])=[CH:30][CH:31]=3)=[O:24])=[CH:20][CH:21]=2)[CH:12]=1)=[O:10])[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67352407Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate

Product 1

HCID 673534913-Methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl) isoxazole-5-carboxamido)butanoic acidYield 76.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate (250 mg) dissolved in THF (5 ml) was added 1 M aqueous solution of Lithium hydroxide monohydrate (1 ml) and stirred at RT for 14 h. The reaction mixture was acidified with dilute HCl and extracted with EtOAc. Organic layer was separated, dried over. Na2SO4 and concentrated under reduced pressure to get off white solid which was crystallized from EtOAc to yield 185 mg (76%) white solid. MS (ES+): m/z 491 (M+1); 1H NMR (DMSO-d6, 300 MHz): δ 12.82 (bs, 1H), 9.22 (s, 1H), 9.12 (s, 1H), 8.93 (d, 1H), 7.85 (d, 2H), 7.68 (s, 1H), 7.65 (d, 2H), 7.61 (d, 2H), 7.56 (d, 2H), 4.26 (m, 1H), 2.21 (m, 1H), 0.95 (d, 6H).

Workup

  1. extractionextracted with EtOAc
  2. customOrganic layer was separated
  3. customdried over
  4. concentrationNa2SO4 and concentrated under reduced pressure
  5. customto get off white solid which
  6. customwas crystallized from EtOAc

Sources & evidence

ORD record
ord-087fed4df0044aa59dcdaa948153bb64
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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