HCID 59607868, compound → HCID 59607872, compound

HRID 70831Notes

Reaction equation

HRID 70831 reaction equation
[CH2:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][C:9]([NH:11][C@H:12]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)=[CH:27][CH:26]=1)[CH2:13][C:14]([O:16]CC1C=CC=CC=1)=[O:15])=[O:10])[CH2:2][CH2:3][CH3:4]>CCOC(C)=O.[Pd]>[CH2:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][C:9]([NH:11][C@H:12]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=2)=[CH:27][CH:26]=1)[CH2:13][C:14]([OH:16])=[O:15])=[O:10])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 1

HCID 59607868HCID 59607868, compound

Product 1

HCID 59607872HCID 59607872, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of (R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3′-chlorobiphenyl-4-yl)butanoate (178.9 mg, 0.334 mmol) and Pd/C (71.0 mg, 0.033 mmol) in EtOAc (3 ml) is allowed to stir under hydrogen at room temperature for 1.5 hours. The reaction mixture is filtered, and concentrated to give crude. The resulting residue is purified by preparative HPLC using a gradient of 20% MeCN/water (0.1% TFA) to 100% MeCN to give (R)-3-(4-butoxy-4-oxobutanamido)-4-(3′-chlorobiphenyl-4-yl)butanoic acid (90.7 mg) as a white solid; HPLC retention time=1.27 minutes (condition B); MS (m+1)=446.24; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.91 (t, J=7.5 Hz, 3 H) 1.31-1.40 (m, 2 H) 1.55-1.62 (m, 2 H) 2.43-2.47 (m, 2 H) 2.52-2.69 (m, 4 H) 2.93 (A of ABX, Jab=13.7 Hz, Jax=7.7 Hz, 1 H) 3.00 (B of ABX, Jab=13.7 Hz, Jbx=6.8 Hz, 1 H) 4.07 (t, J=6.7 Hz, 2 H) 4.49-4.57 (m, 1 H) 6.31 (br d, J=8.6 Hz, 1 H) 7.26-7.37 (m, 4 H) 7.43-7.46 (m, 1 H) 7.49-7.52 (m, 2 H) 7.55 (br t, J=1.8 Hz, 1 H).

Workup

  1. filtrationThe reaction mixture is filtered
  2. concentrationconcentrated
  3. customto give crude
  4. customThe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-3023cf682d7045bea09af472594d12ea
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

Loading…