Hydrochloric Acid → 4-{[(3-cyclopentylpropanoyl)(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)amino]methyl}-N-(4-phenoxybenzyl)benzamide

HRID 902780Notes

Reaction equation

HRID 902780 reaction equation
[CH:1]1([CH2:6][CH2:7][C:8]([N:10]([CH2:24][C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[C:11]2[CH:23]=[CH:22][C:14]3[O:15][C:16]([CH3:21])([CH3:20])[O:17][C:18](=[O:19])[C:13]=3[CH:12]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.[O:49]([C:56]1[CH:63]=[CH:62][C:59]([CH2:60][NH2:61])=[CH:58][CH:57]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.Cl>C1COCC1>[CH:1]1([CH2:6][CH2:7][C:8]([N:10]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:29]([NH:61][CH2:60][C:59]3[CH:62]=[CH:63][C:56]([O:49][C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)=[CH:57][CH:58]=3)=[O:30])=[CH:32][CH:33]=2)[C:11]2[CH:23]=[CH:22][C:14]3[O:15][C:16]([CH3:21])([CH3:20])[O:17][C:18](=[O:19])[C:13]=3[CH:12]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2760343(4-Phenoxyphenyl)methanamineHCID 586936884-{[(3-cyclopentylpropanoyl)(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)amino]methyl}benzoic acid

Product 1

HCID 586936964-{[(3-cyclopentylpropanoyl)(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)amino]methyl}-N-(4-phenoxybenzyl)benzamideYield 81.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-{[(3-cyclopentylpropanoyl)(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)amino]methyl}benzoic acid (212 mg) in THF (2 mL) was added NMM (57 mg). The mixture was chilled at 0° C. and isobutyl chloroformate was added at once (86 mg). The mixture was stirred for 15 min. at 0° C. then 4-phenoxybenzylamine (103 mg) was added and the resulting reaction mixture was stirred 3 h at rt. An aqueous solution oh HCl (1N, 2 mL) was added and the resulting mixture was extracted with Et2O. The combined organic layers were washed with water, brine, dried over MgSO4 filtered and evaporated to give a light yellow oil. Purification by chromatography (SiO2) gave the title compound as a colorless oil (241 mg, 81%). 1H NMR (CDCl3) δ 7.56-7.42 (m, 3H), 7.21-7.00 (m, 6H), 6.95-6.67 (m, 7H), 6.21 (t, J=4.9 Hz, 1H), 4.69 (s, 2H), 4.42 (s, 1H), 4.40 (s, 1H), 1.87 (t, J=7.2 Hz, 2H), 1.54 (s, 6H), 1.48-1.14 (m, 9H), 0.85-0.64 (m, 2M). M+(ESI): 633.0; M−(ESI): 631.0. HPLC, Rt: 5.3 min (purity: 97.7%).

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred 3 h at rt
  3. extractionthe resulting mixture was extracted with Et2O
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a light yellow oil
  9. customPurification by chromatography (SiO2)

Sources & evidence

ORD record
ord-5c0978435b5144baa6fe108317522aca
Source dataset
uspto-grants-2008_04
Patent number
US07365225B2

Reaction notes

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