Hydrochloric Acid → (2S,4S)-4-(3-carboxy-propionylamino)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester

HRID 1188243Notes

Reaction equation

HRID 1188243 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:25])[C@@H:6]([CH3:24])[CH2:7][CH:8]([NH2:23])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:12][CH:11]=1)[CH3:3].[O:26]1[C:30](=[O:31])[CH2:29][CH2:28][C:27]1=[O:32].N1C=CC=CC=1.Cl>C(Cl)Cl>[CH2:2]([O:4][C:5](=[O:25])[C@@H:6]([CH3:24])[CH2:7][C@H:8]([NH:23][C:30](=[O:31])[CH2:29][CH2:28][C:27]([OH:32])=[O:26])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:12][CH:11]=1)[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7922Succinic anhydrideHCID 67505771HCID 67505771, compound

Product 1

HCID 68754940(2S,4S)-4-(3-carboxy-propionylamino)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl esterYield 10.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-4-Amino-5-(3′-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester hydrochloric acid salt (200 mg, 0.52 mmol) and dihydrofuran-2,5-dione (68 mg, 0.68 mmol) in 8 ml CH2Cl2 was added pyridine (0.17 ml, 2.1 mmol) and the solution was stirred for 2 hours. The reaction mixture was acidified to pH=3 with 1M HCl. Solvent was removed under reduced pressure and the residue was purified by preparatory HPLC (DAICEL CHIRALCEL OD-H 21×250 mm column, 18 ml/min, 90% heptane 10% EtOH+0.1% TFA), collected a peak at 5.7 minutes, to give 25 mg (2S,4S)-4-(3-carboxy-propionylamino)-5-(3′-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester. MS m/z 446.3 (M+H), 444.3 (M−H). LC/MS (Condition A): 1.52 min.

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe residue was purified by preparatory HPLC (DAICEL CHIRALCEL OD-H 21×250 mm column, 18 ml/min, 90% heptane 10% EtOH+0.1% TFA)
  3. customcollected a peak at 5.7 minutes

Sources & evidence

ORD record
ord-42b4ee4f48d04483a222d5aba1af39bb
Source dataset
uspto-grants-2014_03
Patent number
US08673974B2

Reaction notes

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