Toluene → HCID 58979111, compound

HRID 1181119Notes

Reaction equation

HRID 1181119 reaction equation
[C:1]([O:5][C:6](=[O:42])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][O:32][C:33](=[O:41])[NH:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[C:1]([O:5][C:6](=[O:42])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([N:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][O:32][C:33](=[O:41])[NH:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 58979035HCID 58979035, compound

Product 1

HCID 58979111HCID 58979111, compoundYield 19.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 1 mL microvial under a nitrogen atmosphere was charged with 3-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}-2-cyclohexylcarbamoyloxymethylphenyl)-propionic acid tert-butyl ester (0.30 g, 0.468 mmol; Example 39), anhydrous toluene (0.5 mL), and then morpholine (0.053 mL, 0.61 mmol). Tris(dibenzylideneacetone)-dipalladium(0) (0.004 g, 0.0044 mmol), 2-(di-tert-butylphosphine)biphenyl (0.006 g, 0.020 mmol), and sodium tert-butoxide (0.063 g, 0.655 mmol) were added sequentially. The mixture was stirred at ambient temperature under a nitrogen atmosphere for 5 h and was poured into EtOAc (50 mL). The organic layer was washed with brine (2×), dried (Na2SO4), and concentrated to a dark yellow oil. This crude product was purified using radial chromatography (EtOAc:hexanes 15:85 to 50:50) to give a yellow oil (0.058 g, 19%). 1H NMR (400 MHz, CDCl3) 1.07-1.18 (m, 3H), 1.29-1.40 (m, 1H), 1.42 (s, 9H), 1.52-1.70 (m, 4H), 1.91-1.93 (m, 2H), 2.34 (s, 3H), 2.46 (t, J=8.1 Hz, 2H), 2.87 (t, J=7.8 Hz, 2H), 2.94 (t, J=6.8 Hz, 2H), 3.24 (t, J=4.9 Hz, 4H), 3.48-3.50 (m, 1H), 3.86 (t, J=4.9 Hz, 4H), 4.20 (t, J=6.6 Hz, 2H), 5.07 (s, 2H), 6.79 (dd, J=8.6, 2.7 Hz, 1H), 6.85-6.93 (m, 3H), 7.09 (d, J=8.3 Hz, 1H), 7.87 (dd, J=11.5, 2.7 Hz, 2H). MS (ES) m/e 648 (M+1).

Workup

  1. washThe organic layer was washed with brine (2×)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated to a dark yellow oil
  4. customThis crude product was purified

Sources & evidence

ORD record
ord-6cffbcad17d44cd3b2f3d128bdd06bd9
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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