Triethylamine → 4-[3-[1(S)-(4-Chlorophenyl)ethyl]1-(4-cyclohexylphenyl)ureidomethyl]benzoic acid methyl ester

HRID 412453Notes

Reaction equation

HRID 412453 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:16]2[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[C:12](=[O:15])[NH:13]Cl)=[CH:6][CH:5]=1.C(N(CC)CC)C.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([C@@H:43](N)[CH3:44])=[CH:39][CH:38]=1>CN1CCCC1=O>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:16]2[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[C:12]([NH:13][C@H:43]([C:40]2[CH:41]=[CH:42][C:37]([Cl:36])=[CH:38][CH:39]=2)[CH3:44])=[O:15])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1550852(S)-(-)-1-(4-chlorophenyl)ethylamineHCID 86586062N-chlorocarbamoyl-4-[(4-cyclohexylphenylamino)methyl]benzoic acid methyl ester

Product 1

HCID 674831604-[3-[1(S)-(4-Chlorophenyl)ethyl]1-(4-cyclohexylphenyl)ureidomethyl]benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 2 L reaction flask equipped with mechanical stirring was charged with N-chlorocarbamoyl-4-[(4-cyclohexylphenylamino)methyl]benzoic acid methyl ester (94 g, 0.244 mol), N-methyl-2-pyrrolidinone (1.0 L) and triethylamine (68 mL, 0.487 mol). To the clear solution was added drop wise (S)-1-(4-chlorophenyl)ethylamine (38.0 g, 0.244 mol), keeping the internal reaction temperature below 30° C. Stirring was continued for 2 hours, then the reaction mixture was partitioned between water (1.0 L) and ethyl acetate (1.0 L). After extensive mixing, the organic layer was separated, and washed with a 5% aqueous solution of citric acid (500 mL), and saturated ammonium chloride (500 mL), before drying with anhydrous sodium sulphate. Solvent was removed, and the residual oil was evaporated once from acetonitrile. This product was sufficiently pure for further synthesis. Yield: 103 g (84%).

Workup

  1. customA 2 L reaction flask
  2. customequipped
  3. customthe internal reaction temperature below 30° C
  4. stirringStirring
  5. customthe reaction mixture was partitioned between water (1.0 L) and ethyl acetate (1.0 L)
  6. customAfter extensive mixing, the organic layer was separated
  7. washwashed with a 5% aqueous solution of citric acid (500 mL), and saturated ammonium chloride (500 mL)
  8. dry with materialbefore drying with anhydrous sodium sulphate
  9. customSolvent was removed
  10. customthe residual oil was evaporated once from acetonitrile
  11. customThis product was sufficiently pure for further synthesis

Sources & evidence

ORD record
ord-a18246657e25463b8b3606869fe3f568
Source dataset
uspto-grants-2003_05
Patent number
US06562807B2

Reaction notes

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