Sodium Hydroxide → (R)-3-(biphenyl-4-ylmethyl)-4-(2-carboxyethylamino)-4-oxobutanoic acid

HRID 70847Notes

Reaction equation

HRID 70847 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([C:13]([NH:15][CH2:16][CH2:17][C:18]([O:20]C)=[O:19])=[O:14])[CH2:9][C:10]([OH:12])=[O:11])=[CH:3][CH:2]=1.[OH-].[Na+]>C1COCC1.CO>[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([C:13]([NH:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[O:14])[CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 59607696(R)-3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoic acid

Product 1

HCID 59607892(R)-3-(biphenyl-4-ylmethyl)-4-(2-carboxyethylamino)-4-oxobutanoic acidYield 76.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoic acid (22.1 mg, 0.060 mmol) in THF (0.6 mL) and methanol (0.1 mL), aqueous 1M NaOH (0.12 mL, 0.12 mmol) is added at room temperature. After stirring for 3 hours, additional aqueous 1M NaOH (0.12 mL, 0.12 mmol) is added. The reaction mixture is allowed to stir for 30 minutes and quenched with 0.5 mL of aqueous 1M HCl and 0.5 mL of brine. The mixture is extracted twice with ethyl acetate, and the organic layer is concentrated under reduced pressure to give (R)-3-(biphenyl-4-ylmethyl)-4-(2-carboxyethylamino)-4-oxobutanoic acid (16.4 mg). HPLC retention time=1.04 minutes (condition A); MS (m+1)=356.1; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.13-2.31 (m, 3 H) 2.59-2.65 (m, 1 H) 2.81-2.90 (m, 2 H) 3.12-3.27 (m, 2 H) 7.26 (d, 2 H, J=8 Hz) 7.34 (t, 1 H, J=7.4 Hz) 7.45 (t, 2 H, J=7.7 Hz) 7.57 (d, 2 H, J=8.1 Hz) 7.63-7.65.

Workup

  1. stirringto stir for 30 minutes
  2. customquenched with 0.5 mL of aqueous 1M HCl and 0.5 mL of brine
  3. extractionThe mixture is extracted twice with ethyl acetate
  4. concentrationthe organic layer is concentrated under reduced pressure

Sources & evidence

ORD record
ord-ebe5197cb05f4a429c11661d9760b0f5
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

Loading…