Hydrochloric Acid → HCID 59607657, compound

HRID 70836Notes

Reaction equation

HRID 70836 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:22][C:23]([C:25]3[O:29][C:28]([O:30]C)=[N:27][CH:26]=3)=[O:24])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C@@H:15]([NH:22][C:23]([C:25]3[O:29][C:28](=[O:30])[NH:27][CH:26]=3)=[O:24])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59607745HCID 59607745, compound

Product 1

HCID 59607657HCID 59607657, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(2-methoxyoxazole-5-carboxamido)butanoate, intermediate 14, (103 mg, 0.23 mmol) in dioxane (3 mL) is added 4 N solution of HCl in dioxane (0.29 mL, 1.16 mmol). The crude was stirred at room temperature for 2 hrs. The crude is concentrated and is diluted in water and EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, and concentrated. 50% of the crude is purified via RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) to give (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(2-oxo-2,3-dihydrooxazole-5-carboxamido)butanoate (38 mg) as a white solid. HPLC retention time=1.66 minutes (condition A); MS (m+1)=429.4; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (t, J=7.1 Hz, 3 H) 2.51-2.69 (m, 2 H) 2.95 (dd, 1 H) 3.05 (dd, 1 H) 4.19 (q, 2 H) 4.58-4.75 (m, 1 H) 6.83 (d, J=8.8 Hz, 1 H) 7.26-7.33 (m, 4 H) 7.35 (t, J=7.7 Hz, 1 H) 7.45 (dt, J=7.6, 1.5 Hz, 1 H) 7.51 (d, J=8.3 Hz, 2 H) 7.56 (t, J=1.8 Hz, 1 H) 8.45 (br. s., 1 H).

Workup

  1. concentrationThe crude is concentrated
  2. additionis diluted in water
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custom50% of the crude is purified via RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-1c1b702b802a468d8f8e87093c2a7f05
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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