4-Chloroaniline → N-(4-Chlorophenyl)-2-cyclopropyl-2-(1-naphthalenyloxy)acetamide

HRID 868835Notes

Reaction equation

HRID 868835 reaction equation
[CH:1]1([CH:4]([O:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11][CH:10]=2)[C:5]([OH:7])=O)[CH2:3][CH2:2]1.[Cl:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.O>[Cl:19][C:20]1[CH:26]=[CH:25][C:23]([NH:24][C:5](=[O:7])[CH:4]([CH:1]2[CH2:2][CH2:3]2)[O:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11][CH:10]=2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 78124-ChloroanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 442198852-Cyclopropyl-2-(1-naphthalenyloxy)acetic acid

Product 1

HCID 44222621N-(4-Chlorophenyl)-2-cyclopropyl-2-(1-naphthalenyloxy)acetamideYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-cyclopropyl-2-(1-naphthalenyloxy)acetic acid (120 mg, 0.49 mmol) and 4-chloroaniline (44.0 μL, 0.49 mmol) in anhydrous DCM (10 mL) under N2 cooled at 0° C. was added EDCI-HCl (187.9 mg, 0.98 mmol) portion wise. The resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×100 mL). The organic extracts were combined, washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using ethyl acetate/n-hexane (a gradient of 5-10%) to furnish 119 (148 mg, 86%) as a white solid. mp 204-206° C.; 1H NMR (CDCl3, 400 MHz) δ 0.65-0.78 (m, 4H0, 1.52 (m, 1H), 4.41 (d, J=6.4 Hz, 1H), 6.70 (d, J=8.0 Hz, 1H), 7.25 (d, J=6.0 Hz, 3H), 7.43 (d, J=8.4 Hz, 2H), 7.61-7.70 (m, 3H), 7.97 (s, 1H), 8.22 (d, J=8.4 Hz, 1H), 8.34 (d, J=8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 2.70, 3.16, 14.42, 82.72, 108.01, 115.68, 121.47, 122.03, 122.96, 127.64, 128.43, 129.28, 129.63, 130.07, 132.96, 135.61, 152.83, 169.27; ESI-HRMS for C21H17ClNO2 (M−H)+calcd. 350.0948. Found 350.0956.

Workup

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. washwashed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c59db77587684ea2ac0bed820d964633
Source dataset
uspto-grants-2015_03
Patent number
US08969342B2

Reaction notes

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