Triethylamine → N-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-isophthalamic acid methyl ester

HRID 2244035Notes

Reaction equation

HRID 2244035 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[NH2:13][C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][CH:34]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[C:21]([OH:28])[C:20]=1[CH2:29][CH2:30][CH3:31].[C:35]([O:46][CH3:47])(=[O:45])[C:36]1[CH:44]=[CH:43][CH:42]=[C:38]([C:39](O)=[O:40])[CH:37]=1.C(N(CC)CC)C>ClCCl>[CH3:47][O:46][C:35](=[O:45])[C:36]1[CH:44]=[CH:43][CH:42]=[C:38]([C:39]([NH:13][C:14]2[CH:34]=[CH:33][CH:32]=[C:16]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[C:21]([OH:28])[C:20]=3[CH2:29][CH2:30][CH3:31])[CH:15]=2)=[O:40])[CH:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 6018803-(Methoxycarbonyl)benzoic acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 145235601-{4-[(3-Aminophenyl)methoxy]-2-hydroxy-3-propylphenyl}ethan-1-one

Product 1

HCID 68429187N-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-isophthalamic acid methyl esterYield 77.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add ethyldimethylaminopropylcarbodiimide hydrochloride (2.47 g, 12.9 mmol) to a solution of 1-[4-(3-amino-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone (1.54 g, 5.14 mmol) and methyl hydrogen isophthalate (1.11 g, 6.17 mmol) in dichloromethane (40 mL) at 0° C. Add triethylamine (3.59 mL, 25.7 mmol) and stir at room temperature for 72 hours. At 5 hours, add additional methyl hydrogen isophthalate (200 mg). Stir overnight. Wash the mixture twice with 2N hydrochloric acid, saturated sodium bicarbonate, brine, dry, and concentrate. Triturate the residue with 1:1 hexanes: dichloromethane, and filter to afford the title compound as an off-white powder (1.83 g, 77%): 1H NMR (CDCl3) δ 0.97 (t, 3H), 1.59 (sextet, 2H), 2.56 (s, 3H), 2.72 (t, 2H), 3.98 (s, 3H), 5.20 (s, 2H), 6.49 (d, 1H), 7.25 (m, 1H), 7.42 (t, 1H), 7.56-7.64 (m, 3H), 7.79 (s, 1H), 7.89 (s, 1H), 8.15 (d, 1H), 8.24 (d, 1H), 8.48 (s, 1H), 12.75 (s, 1H).

Workup

  1. washWash the mixture twice with 2N hydrochloric acid, saturated sodium bicarbonate, brine
  2. customdry
  3. concentrationconcentrate
  4. customTriturate the residue with 1:1 hexanes
  5. filtrationdichloromethane, and filter

Sources & evidence

ORD record
ord-8954963a1eb84750becc878fd0cbc3e5
Source dataset
uspto-grants-2010_03
Patent number
US07678794B2

Reaction notes

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