Lithium hydroxide, monohydrate → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid

HRID 1058440Notes

Reaction equation

HRID 1058440 reaction equation
C[O:2][C:3](=[O:34])/[C:4](/[NH:12][C:13](=[O:33])[C:14]1[C:19]([CH3:20])=[CH:18][C:17]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])=[CH:16][C:15]=1[Cl:32])=[CH:5]/[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.O.[OH-].[Li+]>CO.O1CCCC1.O>[Cl:32][C:15]1[CH:16]=[C:17]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])[CH:18]=[C:19]([CH3:20])[C:14]=1[C:13]([NH:12]/[C:4](=[CH:5]\[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)/[C:3]([OH:34])=[O:2])=[O:33]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 59918708(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl ester

Product 1

HCID 59038386(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acidYield 43%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl ester (Example 212; 23 mg, 0.048 mmol) and lithium hydroxide monohydrate (6 mg, 0.144 mmol) in methanol/tetrahydrofuran/water (2:2:1; 0.25 mL) was stirred at room temperature for 17 h. An second portion of lithium hydroxide monohydrate (2 mg, 0.05 mmol) was added and the solution was stirred for an additional 4 h. The volatiles were removed in vacuo and the residue was taken up in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) and evaporated to dryness. The residue was re-dissolved in the same solvent mixture (1 mL) and applied to a silica gel column. The column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (300:30:10:6) and chloroform/methanol/water/acetic acid (150:30:10:6). The appropriate fractions were combined, evaporated and then lyophilized to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid (9.5 mg, 43% yield) as a colorless powder.

Workup

  1. stirringthe solution was stirred for an additional 4 h
  2. customThe volatiles were removed in vacuo
  3. additionthe residue was taken up in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6)
  4. customevaporated to dryness
  5. dissolutionThe residue was re-dissolved in the same solvent mixture (1 mL)
  6. washThe column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (300:30:10:6) and chloroform/methanol/water/acetic acid (150:30:10:6)
  7. customevaporated

Sources & evidence

ORD record
ord-23ee3cb1e62f492bb07e617d68d6657f
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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