Ethyl Acetate → 3-{4-[3-(4-Benzoyl-phenoxy)-propoxy]-2-cyclohexylcarbamoyloxymethyl-phenyl}-propionic acid tert-butyl ester

HRID 1181133Notes

Reaction equation

HRID 1181133 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][O:17][C:18](=[O:26])[NH:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:29][CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:40])=[CH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(#N)C.O>[C:1]([O:5][C:6](=[O:27])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:29][CH2:30][CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([C:39](=[O:40])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:35][CH:34]=2)=[CH:11][C:10]=1[CH2:16][O:17][C:18](=[O:26])[NH:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19011983[4-(3-Bromopropoxy)phenyl]phenylmethanoneHCID 589789753-(2-Cyclohexylcarbamoyloxymethyl-4-hydroxyphenyl)propionic acid tert-butyl ester

Product 1

HCID 589794473-{4-[3-(4-Benzoyl-phenoxy)-propoxy]-2-cyclohexylcarbamoyloxymethyl-phenyl}-propionic acid tert-butyl esterYield 62.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(2-cyclohexylcarbamoyloxymethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (50 mg, 0.13 mmol; Example 652 Step D), [4-(3-bromo-propoxy)-phenyl]-phenyl-methanone (64 mg, 0.2 mmol, Bull Chem. Soc. Jpn. 1990, 63, 1342) and potassium carbonate (53 mg, 0.39 mmol) in acetonitrile (6 mL) was heated at 80° C. overnight. Ethyl acetate (20 mL) and H2O (20 mL) were added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The crude mixture was purified by silica gel column chromatography (hexane/ethyl acetate 4/1) to give the title compound (50 mg, 62%). 1H-NMR (300 MHz, CDCl3): δ 7.74 (d, 2H, J=8.5), 7.68 (d, 2H, J=7.7), 7.48 (d, 1H, J=8.4), 7.40 (m, 2H), 7.05 (d, 1H, J=8.5), 6.90 (d, 2H, J=8.6), 6.85 (s, 1H), 6.74 (dd, 1H, J=8.5, 2.2), 5.04 (s, 2H), 4.68 (d, 1H, J=7.3), 4.17 (t, 2H, J=5.9), 4.09 (t, 2H, J=5.9), 3.43 (m, 1H), 2.82 (t, 2H, J=7.8), 2.40 (t, 2H, J=7.8), 2.21 (qn, 2H, J=5.9), 1.85 (m, 2H), 1.67-1.02 (m, 8H), 1.36 (s, 9H).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude mixture was purified by silica gel column chromatography (hexane/ethyl acetate 4/1)

Sources & evidence

ORD record
ord-fb51236adafb4f64bcfd20ab3a9d546c
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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