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

HRID 1058428Notes

Reaction equation

HRID 1058428 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].[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]([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: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 23560746Rac.-n-[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Product 1

HCID 59038340(Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1,3,3-Tetramethylguanidine (94 μL, 0.75 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; 244 mg, 0.5 mmol) in tetrahydrofuran (7 mL) at −20° C. After 30 min, quinoline-3-carboxaldehyde (82.5 mg, 0.525 mmol) was added and the solution was stirred at room temperature for 16 h. The solvent was evaporated and ethyl acetate (30 mL) was added. The solution was washed with saturated sodium bicarbonate solution (15 mL) and the aqueous layer was extracted with ethyl acetate (10 mL). Each organic layer was washed with brine. The combined organic layers were dried (MgSO4), filtered, evaporated and chromatographed over silica gel (20-50% ethyl acetate/hexanes) to (Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (221 mg, 86% yield) as an orange-yellow solid.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (30 mL) was added
  3. washThe solution was washed with saturated sodium bicarbonate solution (15 mL)
  4. extractionthe aqueous layer was extracted with ethyl acetate (10 mL)
  5. washEach organic layer was washed with brine
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-04191a5e115c4d6099a4a566df648f31
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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