Hydrochloric Acid → 2,2-Dimethyl-4-{4'-[(4-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}4-oxobutanoic acid

HRID 9603Notes

Reaction equation

HRID 9603 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:23])[CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19]C)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]1[C:30]2[N:31]=[C:32](S(C)(=O)=O)[O:33][C:29]=2[CH:28]=[CH:27][CH:26]=1.[OH-].[Na+].Cl>ClC(Cl)C.CO>[CH3:21][C:16]([CH3:22])([CH2:15][C:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:32]3[O:33][C:29]4[CH:28]=[CH:27][CH:26]=[C:25]([CH3:24])[C:30]=4[N:31]=3)=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)=[O:23])[C:17]([OH:19])=[O:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 219856614-Methyl-2-(methylsulfonyl)-1,3-benzoxazoleHCID 21985743Methyl 4-(4'-amino-1,1'-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate

Product 1

HCID 112932872,2-Dimethyl-4-{4'-[(4-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}4-oxobutanoic acidYield 32.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (74 mg, 0.24 mmol) in dichloroethane (3 mL), 4-methyl-2-(methylsulfonyl)-1,3-benzoxazole (50 mg, 0.24 mmol) was added, and the mixture was heated at 85° C. overnight. The solvent was removed by rotary evaporation and the residue was redissolved in DMF (5 mL). A solution of 1 N aqueous NaOH (0.72 mL, 0.72 mmol) was added, and the mixture was heated at 65° C. overnight. A solution of 1 N aqueous HCl (0.24 mL, 0.24 mmol) and methanol (5 mL) was added to the reaction mixture and the crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 2,2-dimethyl-4-{4′-[(4-methyl-1,3-benzoxazol-2-yl)amino]-1,1′-biphenyl-4-yl}4-oxobutanoic acid as a white solid (32.6 mg, 32.1%). 1H NMR (300 MHz, DMSO-d6) δ 8.00–7.80 (m, 8 H), 7.30 (d, 1 H), 7.05 (d, 2 H), 3.30 (s, 2 H), 2.50 (s, 3 H), 1.10 (s, 6 H); LC-MS ret. time 3.77 min (method 2), m/z 429.2 (MH+).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. dissolutionthe residue was redissolved in DMF (5 mL)
  3. temperaturethe mixture was heated at 65° C. overnight
  4. customthe crude product was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Sources & evidence

ORD record
ord-bf64bfd674a7432d9aea04c6531e87b0
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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