1,1,3,3-Tetramethylguanidine → Rac.-(z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester

HRID 1058430Notes

Reaction equation

HRID 1058430 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])[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].[N:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[C:43]([CH:51]=O)[CH:42]=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])[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:51]/[C:43]1[CH:42]=[N:41][C:50]2[C:45]([CH:44]=1)=[CH:46][CH:47]=[CH:48][CH:49]=2

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 836413-QuinolinecarboxaldehydeHCID 18673037N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59038366Rac.-(z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl esterYield 75%

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-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 134; 120 mg, 0.24 mmol) in tetrahydrofuran (5 mL) at −20° C. After 10 min, quinoline-3-carboxaldehyde (39.3 mg, 0.25 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 (5 mL) and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4), filtered, evaporated and chromatographed over silica gel (50% ethyl acetate/hexanes) to give rac.-(Z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (93 mg, 75% yield) as an off-white solid.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (10 mL) was added
  3. washThe solution was washed with saturated sodium bicarbonate solution (5 mL)
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed over silica gel (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-352d371dbf1543968365d75b0561f464
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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