Hydrochloric Acid → (R)-3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoic acid

HRID 2062155Notes

Reaction equation

HRID 2062155 reaction equation
O[Li].O.C[O:5][C:6](=[O:36])[CH2:7][C@@H:8]([OH:35])[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([CH3:27])=[CH:24][CH:25]=3)[N:20]=[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[OH:34])[N:18]=2)[CH2:13][CH2:12]1)=[O:10].Cl>C1COCC1.O>[OH:35][C@@H:8]([C:9]([N:11]1[CH2:12][CH2:13][N:14]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([CH3:27])=[CH:24][CH:25]=3)[N:20]=[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[OH:34])[N:18]=2)[CH2:15][CH2:16]1)=[O:10])[CH2:7][C:6]([OH:36])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 136121665(R)-methyl 3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoate

Product 1

HCID 136121458(R)-3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoic acidYield 75%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

LiOH.H2O (19.8 mg, 0.47 mmol) was added to a solution of (R)-3-hydroxy-4-{4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-butyric acid methyl ester (71 mg, 0.16 mmol) in 2 mL THF:H2O (1:1) and stirred at room temperature for 3 h. The reaction mixture was acidified with 1 M HCl and then extracted with EtOAc. After drying the organic layer over Na2SO4, it was concentrated and then purified via silica gel chromatography using 0-15% MeOH/CH2Cl2 to provide (R)-3-hydroxy-4-{4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-butyric acid (52 mg, 75%). LC/MS: m/z 437.3 (M+H)+ at 2.04 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialAfter drying the organic layer over Na2SO4, it
  3. concentrationwas concentrated
  4. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-b9ab76eb3a5945a98ac953595f27f20e
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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