Hydrochloric Acid → HCID 178461717, compound

HRID 1469624Notes

Reaction equation

HRID 1469624 reaction equation
C([O:3][C:4](=[O:32])[C@H:5]([CH3:31])[CH2:6][C@H:7]([NH:22][C:23]([C:25]1[O:29][N:28]=[C:27]([OH:30])[CH:26]=1)=[O:24])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+].Cl>C(O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([CH2:8][C@@H:7]([NH:22][C:23]([C:25]3[O:29][N:28]=[C:27]([OH:30])[CH:26]=3)=[O:24])[CH2:6][C@@H:5]([CH3:31])[C:4]([OH:32])=[O:3])=[CH:10][CH:11]=2)[CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178472552HCID 178472552, compound

Product 1

HCID 178461717HCID 178461717, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Next, to a solution of (2R,4S)-5-(3′-chloro-biphenyl-4-yl)-4-[(3-hydroxy-isoxazole-5-carbonyl)-amino]-2-methyl-pentanoic acid ethyl ester (73 mg, 0.16 mmol) in ethanol (4 mL) is added 1N NaOH (2 mL) and the resulting mixture is stirred at room temperature for 2 hours. The mixture is acidified with 1N HCl and the solvent is removed under reduced pressure. The resulting residue is purified by preparative HPLC using a gradient of 10% MeCN/water to 100% MeCN (0.1% TFA) to give (2R,4S)-5-(3′-chloro-biphenyl-4-yl)-4-[(3-hydroxy-isoxazole-5-carbonyl)-amino]-2-methyl-pentanoic acid; HPLC Retention time 1.05 minutes (condition C): MS 429.1 (M+1); 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (d, 3 H) 1.58 (ddd, J=13.89, 9.98, 4.42 Hz, 1 H) 1.87 (ddd, J=13.71, 9.66, 3.92 Hz, 1 H) 2.41 (ddd, J=9.54, 7.14, 4.55 Hz, 1 H) 2.82 (dd, J=6.69, 3.41 Hz, 2 H) 4.10-4.24 (m, 1 H) 6.50 (s, 1 H) 7.28 (d, J=8.34 Hz, 2 H) 7.36-7.42 (m, 1 H) 7.47 (t, J=7.83 Hz, 1 H) 7.58-7.65 (m, 3 H) 7.70 (t, J=1.89 Hz, 1 H) 8.66 (d, J=8.59 Hz, 1 H).

Workup

  1. customthe solvent is removed under reduced pressure
  2. customThe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-9ea26d2c518047cb930478529afc8d7b
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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