1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester

HRID 1058429Notes

Reaction equation

HRID 1058429 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:40])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:31])[CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[CH:17][C:16]=1[Cl:32].[CH3:41][C:42]1[S:43][C:44]([CH:48]=O)=[C:45]([CH3:47])[N:46]=1>O1CCCC1>[CH3:9][O:10][C:11](=[O:40])/[C:12](/[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:31])[CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[CH:17][C:16]=1[Cl:32])=[CH:48]/[C:44]1[S:43][C:42]([CH3:41])=[N:46][C:45]=1[CH3:47]

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 27762492,4-Dimethyl-1,3-thiazole-5-carbaldehydeHCID 23560746Rac.-n-[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59038456(Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-N-[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 133; 116 mg, 0.24 mmol) in tetrahydrofuran (6 mL) at −20° C. After 15 min, 2,4-dimethylthiazole-5-carboxaldehyde (Example 43; 37 mg, 0.26 mmol) was added and the solution was stirred at room temperature for 16 h. The solvent was evaporated and ethyl acetate (15 mL) was added. The resulting solution was washed with saturated sodium bicarbonate solution (15 mL) and brine. The organic layer was dried (MgSO4), filtered, evaporated, chromatographed over silica gel (60% ethyl acetate/hexanes) and crystallized from diethyl ether/hexanes to (Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester (98 mg, 82% yield) as a colorless solid.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (15 mL) was added
  3. washThe resulting solution was washed with saturated sodium bicarbonate solution (15 mL) and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed over silica gel (60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-03fc82e92689400e9b7c6643e83951f3
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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