Sodium Hydroxide → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acid

HRID 1058448Notes

Reaction equation

HRID 1058448 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:38])/[C:6](/[NH:17][C:18](=[O:37])[C:19]1[CH:24]=[CH:23][C:22]([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:21][C:20]=1[Cl:36])=[CH:7]/[C:8]1[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=1[CH3:16]>CO.O1CCCC1>[Cl:36][C:20]1[CH:21]=[C:22]([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:23]=[CH:24][C:19]=1[C:18]([NH:17]/[C:6](=[CH:7]\[C:8]1[S:12][C:11]([CH:13]([CH3:14])[CH3:15])=[N:10][C:9]=1[CH3:16])/[C:5]([OH:38])=[O:4])=[O:37]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59038367(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acid methyl ester

Product 1

HCID 59038320(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acidYield 65%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

An aqueous 1N solution of sodium hydroxide (1 mL, 1 mmol) was added to a solution of (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl)]propenoic acid methyl ester (Example 233; 65 mg, 0.123 mmol) in methanol/tetrahydrofuran (1:1; 2 mL). The solution was stirred at room temperature for 18 h, then at 50° C. for 6 h and finally at room temperature for 16 h. The reaction mixture was evaporated to dryness and after the addition of water the solution was acidified with 1N hydrochloric acid solution. The gelatinous colorless solid that precipitated was recovered by filtration and washed thoroughly with water. It was re-suspended in water and lyophilized. The obtained tacky material was dissolved in methanol (0.25 mL) and treated to constant turbidity with water. The resulting off-white solid was filtered off, washed with water/methanol (9:1) and dried in vacuo (45° C., 66 h) to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[2-(1-methylethyl)-4-methylthiazol-5-yl]propenoic acid (41 mg, 65% yield) as an off-white powder.

Workup

  1. waitat 50° C. for 6 h
  2. waitfinally at room temperature for 16 h
  3. customThe reaction mixture was evaporated to dryness
  4. additionafter the addition of water the solution
  5. filtrationThe gelatinous colorless solid that precipitated was recovered by filtration
  6. washwashed thoroughly with water
  7. dissolutionThe obtained tacky material was dissolved in methanol (0.25 mL)
  8. additiontreated to constant turbidity with water
  9. filtrationThe resulting off-white solid was filtered off
  10. washwashed with water/methanol (9:1)
  11. customdried in vacuo (45° C., 66 h)

Sources & evidence

ORD record
ord-207e8042afe542109f48041fdaecd872
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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