Lithium hydroxide, monohydrate → (R)-3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoic acid

HRID 2079303Notes

Reaction equation

HRID 2079303 reaction equation
[OH:1][C@@H:2]([C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[OH:33])[N:17]=2)[CH2:12][CH2:11]1)=[O:9])[CH2:3][C:4]([O:6]C)=[O:5].O[Li].O>C1COCC1.O>[OH:1][C@@H:2]([C:8]([N:10]1[CH2:11][CH2:12][N:13]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[OH:33])[N:17]=2)[CH2:14][CH2:15]1)=[O:9])[CH2:3][C:4]([OH:6])=[O:5]

Participants

4

Reactant 2

HCID 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 88%

Reagents, catalysts & solvents 1

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

Procedure

(R)-Methyl 3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoate (88 mg, 0.20 mmol) and LiOH.H2O (33 mg, 0.78 mmol) were stirred in THF:H2O 1:1 at room temperature for 3 h. After acidification with 1 M HCl and extraction with EtOAc, the organic extracts were washed with water, dried over Na2SO4, and concentrated. The crude material was then purified via silica gel chromatography using 0-10% MeOH/CH2Cl2 to obtain (R)-3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoic acid (75 mg, 88%). LC/MS: m/z 437.3 (M+H)+ at 2.04 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. extractionAfter acidification with 1 M HCl and extraction with EtOAc
  2. washthe organic extracts were washed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was then purified via silica gel chromatography

Sources & evidence

ORD record
ord-7edb471e43634c16940bb390ffbcacee
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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