1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2(S)-methoxy-N[1(S)-(2-naphthyl)propyl]-2-phenylacetamide

HRID 635631Notes

Reaction equation

HRID 635631 reaction equation
[CH3:1][O:2][C@@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.ON1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2N=N1.CN(C)[CH2:25][CH2:26][CH2:27][N:28]=C=NCC>ClCCl>[CH3:1][O:2][C@@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([NH:28][C@H:27]([C:21]1[CH:20]=[CH:19][C:18]2[C:17](=[CH:4][CH:3]=[CH:7][CH:8]=2)[CH:22]=1)[CH2:26][CH3:25])=[O:6]

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 643325(+)-Methoxyphenylacetic acid

Product 1

HCID 700941162(S)-methoxy-N[1(S)-(2-naphthyl)propyl]-2-phenylacetamideYield 94.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1.3 g (7.03 mmol) of (RS)-ethyl-2-naphthalenemethylamine, 1 g (6.02 mmol) of (S)-(+)-α-methoxyphenylacetic acid, 1.1 g (8.15 mmol) of 1-hydroxybenzotriazole and 1.4 g (7.31 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide was stirred in 20 ml of dichloromethane for 18 hours. The solution was extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution, then dried over magnesium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel using 25% ethyl acetate in petroleum ether and then 33% ethyl acetate in petroleum ether for the elution. After trituration with 50% diethyl ether in petroleum ether there were obtained 950 mg of 2(S)-methoxy-N[1(S)-(2-naphthyl)propyl]-2-phenylacetamide, 1H NMR (400 MHz, DMSO) δ: 0.8-0.85 (t,3H), 1.8-1.9 (m,2H), 3.3 (s,3H), 4.7 (s,1H), 4.8-4.9 (q,1H),7.25-7.5 (m,8H), 7.68 (s,1H), 7.75-7.9 (m,3H), 8.5-8.6 (d,1H), which was eluted first, and 850 mg of 2(S)methoxy-N-[1(R)-(2-naphthyl)propyl]-2-phenylacetamide, 1H NMR (400 MHz, DMSO) δ: 0.8-0.9 (t,3H), 1.75-1.9 (m,2H), 3.3 (s,3H), 4.7 (s,1H), 4.8-4.9 (q,1H), 7.25-7.5 (m,8H), 7.7 (s,1H), 7.75-7.9 (m,3H), 8.5-8.6 (d,1H), which was eluted subsequently.

Workup

  1. extractionThe solution was extracted with 2M hydrochloric acid and saturated sodium bicarbonate solution
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe residue was chromatographed on silica gel using 25% ethyl acetate in petroleum ether
  6. wash33% ethyl acetate in petroleum ether for the elution

Sources & evidence

ORD record
ord-cef7cdc903c543a994fbe9cd9d354549
Source dataset
uspto-grants-2001_02
Patent number
US06187905B1

Reaction notes

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