(R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3'-chlorobiphenyl-4-yl)butanoate → HCID 59607872, compound

HRID 881814Notes

Reaction equation

HRID 881814 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 59607868(R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3'-chlorobiphenyl-4-yl)butanoate

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 (Example 3-3: 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-8f6f81f6549c4bc584b2bc7f2167cbdb
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Reaction notes

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