Ethyl Acetate → HCID 178438578, compound

HRID 2048554Notes

Reaction equation

HRID 2048554 reaction equation
[O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][CH:28]=[C:4]2[N:3]1[C@H:29]1[CH2:34][CH2:33][C@H:32]([O:35][CH2:36][C:37](=[O:39])[CH3:38])[CH2:31][CH2:30]1.[CH2:40]([Si:42](Cl)([CH2:45][CH3:46])[CH2:43][CH3:44])[CH3:41].[CH3:48][Si](C)(C)[N-][Si](C)(C)C.[Li+].C(OCC)(=O)C>O1CCCC1>[CH3:38][C:37]1([O:39][Si:42]([CH2:45][CH3:46])([CH2:43][CH3:44])[CH2:40][CH3:41])[CH2:48][CH:36]1[O:35][C@H:32]1[CH2:31][CH2:30][C@H:29]([N:3]2[C:2](=[O:1])[C:7]([CH2:8][C:9]3[CH:10]=[CH:11][C:12]([C:15]4[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=4)=[CH:13][CH:14]=3)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]3[N:26]=[CH:27][CH:28]=[C:4]23)[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 13819ChlorotriethylsilaneHCID 2733832Lithium HexamethyldisilazideHCID 178438630HCID 178438630, compound

Product 1

HCID 178438578HCID 178438578, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4′-({5-oxo-4-[trans-4-(2-oxopropoxy)cyclohexyl]-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (1.12 g) and triethylsilyl chloride (0.72 mL) in tetrahydrofuran (15 mL) was added dropwise lithium hexamethyldisilazide (1.1 M tetrahydrofuran solution, 2.9 mL) at −78° C., and the mixture was stirred for 2 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in methylene chloride (5 mL), and the solution was added dropwise to a solution of diethylzinc (1 M hexane solution, 15 mL) and chloroiodomethane (1.09 mL) in methylene chloride (20 mL) at 0° C., and the mixture was stirred for 2 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.44 g, 31%).

Workup

  1. extractionsaturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methylene chloride (5 mL)
  6. additionthe solution was added dropwise to a solution of diethylzinc (1 M hexane solution, 15 mL) and chloroiodomethane (1.09 mL) in methylene chloride (20 mL) at 0° C.
  7. stirringthe mixture was stirred for 2 hr
  8. additionTo the reaction mixture were added ethyl acetate
  9. extractionsaturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c58f12a1df62499cabc4e09c6121c1af
Source dataset
uspto-grants-2013_11
Patent number
US08592431B2

Reaction notes

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