Sodium Hydroxide → (R)-4-(1-carboxy-3-(3'-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid

HRID 1945031Notes

Reaction equation

HRID 1945031 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([NH:23][C:24](=[O:30])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:17][C:18]([O:20]CC)=[O:19])=[CH:11][CH:10]=1.[OH-].[Na+]>C1COCC1.CO>[C:18]([CH2:17][C@H:16]([NH:23][C:24](=[O:30])[CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:3]2[CH:2]=[CH:7][CH:6]=[C:5]([Cl:8])[CH:4]=2)=[CH:10][CH:11]=1)([OH:20])=[O:19]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59607718HCID 59607718, compound

Product 1

HCID 59607741(R)-4-(1-carboxy-3-(3'-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acidYield 70.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-4-(1-(2′,5′-dichlorobiphenyl-4-yl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (106 mg, 0.234 mmol) in THF (2 ml) and MeOH (0.1 ml), 1M aqueous NaOH solution (1.406 mL, 1.406 mmol) is added at room temperature. After stirring for 4.5 hours, the reaction is quenched with 0.1 M aqueous HCl (3 ml), and the products are extracted with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude is triturated in DCM. The precipitates are collected on a funnel, washed with DCM, and dried under reduced pressure to give (R)-4-(1-carboxy-3-(3′-chlorobiphenyl-4-yl)propan-2-ylamino)-4-oxobutanoic acid (64.0 mg) as white solid; HPLC retention time=1.24 minutes (condition A); MS (m+1)=424.07; 1H NMR (400 MHz, CD3OD) δ ppm 2.38-2.42 (m, 2H) 2.45-2.57 (m, 4H) 2.87 (A of ABX, Jab=13.6 Hz, Jax=7.6 Hz, 1H) 2.95 (B of ABX, Jab=13.6 Hz, Jbx=6.1 Hz, 1H) 4.44-4.51 (m, 1H) 7.30-7.37 (m, 6H) 7.47 (d, J=8.4 Hz, 1H).

Workup

  1. customthe reaction is quenched with 0.1 M aqueous HCl (3 ml)
  2. extractionthe products are extracted with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude is triturated in DCM
  8. customThe precipitates are collected on a funnel
  9. washwashed with DCM
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-a2237388caf646008f6aea17daef75b7
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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