Cesium carbonate → 3-{2-Cyclohexylcarbamoyloxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propionic acid tert-butyl ester

HRID 1181117Notes

Reaction equation

HRID 1181117 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].[CH3:28][C:29]1[O:33][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[N:31][C:30]=1[CH2:40][CH2:41]OS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6](=[O:27])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:41][CH2:40][C:30]2[N:31]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:33][C:29]=2[CH3:28])=[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

5

Reactant 3

HCID 10796Cesium carbonateHCID 120517392-(5-Methyl-2-phenyloxazol-4-yl)ethyl 4-methylbenzenesulfonateHCID 589789753-(2-Cyclohexylcarbamoyloxymethyl-4-hydroxyphenyl)propionic acid tert-butyl ester

Product 1

HCID 589795173-{2-Cyclohexylcarbamoyloxymethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propionic acid tert-butyl esterYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A 40 mL Carousel tube was charged with 3-(2-cyclohexylcarbamoyloxymethyl-4-hydroxyphenyl)propionic acid tert-butyl ester (0.10 g, 0.26 mmol) in anhydrous DMF (1.0 mL). Toluene-4-sulfonic acid 2-(5-methyl-2-phenyloxazol-4-yl)ethyl ester (0.104 g, 0.292 mmol) and cesium carbonate (0.13 g, 0.40 mmol) were added. The mixture was stirred and heated at 55° C. under a nitrogen atmosphere for 30 h and was concentrated. The residue was diluted with EtOAc (50 mL) and washed twice with brine (2×), dried (Na2SO4), and concentrated. The crude residue was purified using radial chromatography (EtOAc: CH2Cl2 2:98 to 5:95) to give a white solid (0.085 g, 57%). 1H NMR (400 MHz, CDCl3) 1.07-1.19 (m, 3H), 1.24-1.38 (m, 2H), 1.42 (s, 9H), 1.56-1.60 (m, 1H), 1.67-1.70 (m, 2H), 1.91-1.93 (m, 2H), 2.37 (s, 3H), 2.46 (t, J=7.8 Hz, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.96 (t, J=7.8 Hz, 2H), 3.48-3.50 (m, 1H), 4.22 (t, J=6.8 Hz, 2H), 4.69-4.71 (m, 1H), 5.07 (s, 2H), 6.80 (dd, J=8.3, 2.4 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 7.10 (d, J=8.3 Hz, 1H), 7.39-7.45 (m, 3H), 7.98 (dd, J=4.2, 2.2 Hz, 2H). MS (ES) m/e 563 (M+1).

Workup

  1. concentrationwas concentrated
  2. additionThe residue was diluted with EtOAc (50 mL)
  3. washwashed twice with brine (2×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified

Sources & evidence

ORD record
ord-9063f38d0f4140c080a889c18d211e30
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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