Hydrochloric Acid → (R)-2-(5-((S)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoic acid

HRID 1161261Notes

Reaction equation

HRID 1161261 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH3:31])[C:9]([NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH:14]=[CH:15][N:16]([C@H:23]([CH:28]([CH3:30])[CH3:29])[C:24]([O:26]C)=[O:25])[C:17]3=[O:22])=[O:10])=[CH:4][CH:3]=1.[OH-].[Li+].C(O)(C)(C)C.O.Cl>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH3:31])[C:9]([NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH:14]=[CH:15][N:16]([C@H:23]([CH:28]([CH3:30])[CH3:29])[C:24]([OH:26])=[O:25])[C:17]3=[O:22])=[O:10])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 6386tert-ButanolHCID 59515742(R)-Methyl 2-(5-((S)-2-(4-chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate

Product 1

HCID 59515709(R)-2-(5-((S)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoic acid

Procedure

(R)-methyl 2-(5-((S)-2-(4-chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate (0.43 g, 0.00088 mol) was stirred with lithium hydroxide (0.05 g, 0.002 mol) in tert-butyl alcohol (6 mL, 0.06 mol) and water (3 mL, 0.2 mol) at 0° C. for 1 hour. 1 N HCl was added until pH<7 and then reaction mixture was extracted with CH2Cl2 (40 mL×3). The organic layers were dried over MgSO4, filtered, purified via flash chromatography (12 g of silica gel, 0-50% EtOAc/Hexane) and gave a light yellow solid. 1H NMR δ (CDCl3) δ: 8.17 (br, 1H), 7.86 (br, 1H), 7.52-7.29 (m, 6H), 7.03 (br, 1H), 6.09-6.05 (m, 1H), 5.00-4.87 (m, 1H), 3.87-3.82 (m, 1H), 2.70-2.60 (m, 1H), 1.64 (d, J=7.0 Hz, 3H), 1.14 (d, J=6.5 Hz, 3H), 0.78 (d, J=6.4 Hz, 3H). MS m/z 427.1 (M+H)+.

Workup

  1. customreaction mixture
  2. extractionwas extracted with CH2Cl2 (40 mL×3)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. custompurified via flash chromatography (12 g of silica gel, 0-50% EtOAc/Hexane)
  6. customgave a light yellow solid

Sources & evidence

ORD record
ord-45bb303afd1b48fca87c566b60210e9e
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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