Acetic Acid → HCID 46853081, compound

HRID 2199701Notes

Reaction equation

HRID 2199701 reaction equation
[Li+].[OH-].[Cl:3][C:4]1[CH:5]=[C:6]([C:41]#[N:42])[C:7]2[S:11][CH:10]=[C:9]([CH:12]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=3)[C@@H:13]([C:17]3[CH:32]=[CH:31][C:20]([C:21]([NH:23][CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])=[O:22])=[CH:19][CH:18]=3)[CH2:14][CH2:15][CH3:16])[C:8]=2[CH:40]=1.C(O)(=O)C>C1COCC1>[Cl:3][C:4]1[CH:5]=[C:6]([C:41]#[N:42])[C:7]2[S:11][CH:10]=[C:9]([CH:12]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=3)[C@@H:13]([C:17]3[CH:32]=[CH:31][C:20]([C:21]([NH:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:22])=[CH:19][CH:18]=3)[CH2:14][CH2:15][CH3:16])[C:8]=2[CH:40]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 67003511HCID 67003511, compound

Product 1

HCID 46853081HCID 46853081, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of LiOH (2.0 M in water, 4.5 mL, 9.0 mmol) was added to a solution of ethyl N-(4-{(1S)-1-[(5-chloro-7-cyano-1-benzothien-3-yl)(4-chlorophenyl)methyl]butyl}benzoyl)-β-alaninate (0.100 g, 0.168 mmol) in THF (9.0 mL). The mixture was stirred at room temperature for four hours then acidified with acetic acid and extracted with ethyl acetate. The organics were dried over Na2SO4, filtered, then concentrated. The resulting residue was purified by reverse-phase HPLC eluting with 20-100% acetonitrile/water containing 0.1% TFA. Following lyophilization, the material was further purified by silica gel chromatography eluting with 5% MeOH in DCM containing 0.5% acetic acid to afford the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.77 (br s, 1H); 7.60 (d, J=5 Hz, 2H); 7.52 (br s, 1H); 7.42 (br s, 1H); 7.31-7.35 (m, 4H); 7.25 (d, J=7 Hz, 2H); 6.78 (br s, 1H); 4.49 (d, J=11 Hz, 1H); 3.67 (br s, 2H); 3.44-3.47 (m, 1H); 2.66 (br, 2H); 1.45-1.53 (m, 2H); 0.98-1.05 (m, 2H); 0.73 (t, J=7 Hz, 3H). LC1: 3.97 min. (M+H)+ 565.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by reverse-phase HPLC
  6. washeluting with 20-100% acetonitrile/water containing 0.1% TFA
  7. customthe material was further purified by silica gel chromatography
  8. washeluting with 5% MeOH in DCM containing 0.5% acetic acid

Sources & evidence

ORD record
ord-002ea04bcad84ff7a6446efd11913c0d
Source dataset
uspto-grants-2016_06
Patent number
US09359339B2

Reaction notes

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