Benzaldehyde → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl ester

HRID 1058423Notes

Reaction equation

HRID 1058423 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:41])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28](O)[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33].[CH:42](=O)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.[O:50]1CCCC1>>[CH3:9][O:10][C:11](=[O:41])/[C:12](/[NH:13][C:14](=[O:34])[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([C:22]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([OH:50])[CH:27]=2)=[O:23])=[CH:17][C:16]=1[Cl:33])=[CH:42]/[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 4

HCID 240BenzaldehydeHCID 8028TetrahydrofuranHCID 664601,1,3,3-TetramethylguanidineHCID 23560749Rac.-n-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59918708(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl esterYield 73%

Procedure

1,1,3,3-Tetramethylguanidine (20 μL, 0.16 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 132; 33 mg, 0.066 mmol) in tetrahydrofuran (1 mL) at room temperature. After 5 min, benzaldehyde (7 μL, 0.068 mmol) was added and the solution was stirred at room temperature for 16 h. The solvent was evaporated and the residue was purified by chromatography over silica gel. The column was eluted sequentially 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 fractions were combined and lyophilized to fuirnish (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl ester (23 mg, 73% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by chromatography over silica gel
  3. washThe column was eluted sequentially 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)

Sources & evidence

ORD record
ord-21ea2983cd844e279a4e86c696556c75
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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