Triethylamine → Ethyl 2-[4-methoxy-3-({[4-(trifluoromethyl)benzoyl]amino}methyl)benzyl]butanoate

HRID 1826086Notes

Reaction equation

HRID 1826086 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.Cl.[CH2:28]([CH:30]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([CH2:45][NH2:46])[CH:38]=1)[C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH3:29]>ClCCl>[CH2:28]([CH:30]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([CH2:45][NH:46][C:7](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=2)[CH:38]=1)[C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH3:29]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 99664-(Trifluoromethyl)benzoic acidHCID 10928Ethyl chloroformateHCID 22139981Ethyl 2-[(3-aminomethyl-4-methoxyphenyl)-methyl]butyrate hydrochloride

Product 1

HCID 11004633Ethyl 2-[4-methoxy-3-({[4-(trifluoromethyl)benzoyl]amino}methyl)benzyl]butanoateYield 93.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(trifluoromethyl)benzoic acid (114 mg, 0.600 mmol) and triethylamine (0.21 mL, 1.51 mmol) in dichloromethane (3 mL), ethyl chlorocarbonate (0.063 mL, 0.659 mmol) was added under stirring and cooling with ice, and the mixture was stirred for 20 minutes. Next, after ethyl 2-ethyl-3-[3-(aminomethyl)-4-methoxyphenyl]propanoate hydrochloride (200 mg, 0.663 mmol) was added, the mixture was stirred for 1 hour under cooling with ice and for 3 hours at room temperature. Dichloromethane (20 mL) was added to the reaction mixture, which was washed with 1 mol/L hydrochloric acid, saturated aqueous solution of sodium hydrogencarbonate and brine, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=4:1 v/v) to afford 245 mg (93%) of the title compound as colorless crystals.

Workup

  1. temperaturecooling with ice
  2. stirringthe mixture was stirred for 20 minutes
  3. stirringthe mixture was stirred for 1 hour
  4. washwas washed with 1 mol/L hydrochloric acid, saturated aqueous solution of sodium hydrogencarbonate and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (eluent: n-hexane:ethyl acetate=4:1 v/v)

Sources & evidence

ORD record
ord-a4c6184cdd674d08b7da1aa97b5c970f
Source dataset
uspto-grants-2006_05
Patent number
US07049342B2

Reaction notes

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