1,1,3,3-Tetramethylguanidine → HCID 59038467, compound

HRID 1058433Notes

Reaction equation

HRID 1058433 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]([CH:21]([OH:31])/[CH:22]=[CH: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]([CH:21]([OH:31])/[CH:22]=[CH: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 23560741HCID 23560741, compound

Product 1

HCID 59038467HCID 59038467, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-(E)-N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 135; 116 mg, 0.24 mmol) in tetrahydrofuran (5 mL) at −20° C. After 10 min, 2,4-dimethylthiazole-5-carboxaldehyde (Example 43; 36 mg, 0.255 mmol) was added and the solution was stirred at room temperature for 16 h. The solvent was evaporated and ethyl acetate (10 mL) was added. The solution was washed with saturated sodium bicarbonate solution (10 mL) and brine (10 mL). Each aqueous layer was extracted with ethyl acetate (10 mL). The combined organic layers were dried, filtered, evaporated and chromatographed (60% ethyl acetate/hexanes) to give rac.-(Z)-2-[[2-chloro-4-[(E)-1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester (101 mg, 84% yield) as a colorless oil.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (10 mL) was added
  3. washThe solution was washed with saturated sodium bicarbonate solution (10 mL) and brine (10 mL)
  4. extractionEach aqueous layer was extracted with ethyl acetate (10 mL)
  5. customThe combined organic layers were dried
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed (60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fd184921dc6a44f9a95f1d60ee377a85
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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