Water → HCID 178464148, compound

HRID 1170440Notes

Reaction equation

HRID 1170440 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.CCCCCC.C([Li])CCC.[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[C:25]1([O:50][Si:51]([CH2:56][CH3:57])([CH2:54][CH3:55])[CH2:52][CH3:53])[C:33]2[C:28](=[CH:29][C:30](I)=[CH:31][C:32]=2[C:34]([F:37])([F:36])[F:35])[N:27]([CH2:39][C@H:40]2[CH2:43][C@H:42]([N:44]([CH2:47][CH3:48])[CH2:45][CH3:46])[CH2:41]2)[C:26]1=[O:49].O>O1CCCC1>[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[C:25]1([O:50][Si:51]([CH2:56][CH3:57])([CH2:52][CH3:53])[CH2:54][CH3:55])[C:33]2[C:28](=[CH:29][C:30]([C:2]3[O:1][CH:5]=[CH:4][N:3]=3)=[CH:31][C:32]=2[C:34]([F:36])([F:35])[F:37])[N:27]([CH2:39][C@H:40]2[CH2:41][C@H:42]([N:44]([CH2:45][CH3:46])[CH2:47][CH3:48])[CH2:43]2)[C:26]1=[O:49]

Participants

6

Reactant 4

HCID 962WaterHCID 9255OxazoleHCID 178418244HCID 178418244, compoundHCID 178464149HCID 178464149, compound

Product 1

HCID 178464148HCID 178464148, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of oxazole (150 mg, 2.17 mmol) in tetrahydrofuran (4 mL) was added 2.67 M n-butyl lithium hexane solution (0.8 mL, 2.14 mmol) at −78° C. under nitrogen, and the mixture was stirred for 15 minutes. To the reaction solution was added 1.0M zinc chloride diethyl ether solution (2.2 mL, 2.2 mmol) at −78° C., and the mixture was stirred for 15 minutes. The reaction solution was allowed to warm to 0° C., and then thereto was added a solution of the compound of Example 14-1 (310 mg, 0.418 mmol) and tetrakistriphenylphosphine palladium (20 mg, 0.017 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 1 hour, and then the mixture was heated to stir at 60° C. for 3 hours. To the reaction solution was added water, and the mixture was extracted with ethyl acetate, and then the organic layer was washed with saturated saline, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography (chloroform/methanol=20/1) to give the titled compound (160 mg, 56%).

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. stirringthe mixture was stirred at room temperature for 1 hour
  3. temperaturethe mixture was heated
  4. stirringto stir at 60° C. for 3 hours
  5. extractionthe mixture was extracted with ethyl acetate
  6. washthe organic layer was washed with saturated saline
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by silica gel chromatography (chloroform/methanol=20/1)

Sources & evidence

ORD record
ord-7e669ee2c6ed4ffb9650cf63a8e6153d
Source dataset
uspto-grants-2010_11
Patent number
US07825155B2

Reaction notes

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