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

HRID 1058439Notes

Reaction equation

HRID 1058439 reaction equation
C[O:2][C:3](=[O:38])/[C:4](/[NH:16][C:17](=[O:37])[C:18]1[C:23]([CH3:24])=[CH:22][C:21]([C:25]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([OH:35])[CH:30]=2)=[O:26])=[CH:20][C:19]=1[Cl:36])=[CH:5]/[C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2.O.[OH-].[Li+]>CO.O1CCCC1.O>[Cl:36][C:19]1[CH:20]=[C:21]([C:25]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([OH:35])[CH:30]=2)=[O:26])[CH:22]=[C:23]([CH3:24])[C:18]=1[C:17]([NH:16]/[C:4](=[CH:5]\[C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)/[C:3]([OH:38])=[O:2])=[O:37]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 59918694(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester

Product 1

HCID 23560642(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acidYield 58.1%

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-(quinolin-3-yl)propenoic acid methyl ester (Example 211; 32 mg, 0.06 mmol) and lithium hydroxide monohydrate (11 mg, 0.262 mmol) in methanol/tetrahydrofuran/water (2:2:1; 0.25 mL) was stirred at room temperature for 48 h. An additional portion of lithium hydroxide monohydrate (6 mg, 0.14 mmol) was added and the solution was stirred for an additional 4 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) and re-evaporated. A solution of the residual material in the same solvent mixture (1 mL) was applied to a silica gel column. The column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6). The appropriate homogeneous fractions were combined, evaporated and then lyophilized to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid (18 mg, 58% yield).

Workup

  1. stirringthe solution was stirred for an additional 4 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6)
  4. customre-evaporated
  5. washThe column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6)
  6. customevaporated

Sources & evidence

ORD record
ord-4c585577adb54555903c1b8f3ddc3fad
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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