Tetrahydrofuran → HCID 68580195, compound

HRID 645455Notes

Reaction equation

HRID 645455 reaction equation
Br[CH2:2][CH:3]=[CH:4][C:5]1([CH3:31])[CH2:9][CH2:8][CH:7]([CH2:10][O:11][Si:12]([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:6]1([CH3:30])[CH3:29].[NH4+].[Cl-].[NH4+].[OH-].[CH2:36]1COCC1>>[C:25]([Si:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[O:11][CH2:10][CH:7]1[CH2:8][CH2:9][C:5]([CH3:31])([CH:4]([CH3:36])[CH:3]=[CH2:2])[C:6]1([CH3:30])[CH3:29])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 68580433HCID 68580433, compound

Product 1

HCID 68580195HCID 68580195, compoundYield 79%

Conditions

Temperature
-55 °C

Procedure

To Me2S.CuBr (dried twice by azeotropic distillation with toluene; 5.04 g, 24.02 mmol) in dry THF (40 mL ) at −78° C. was added dropwise CH3Li (1.4 M solution in Et2O; 34.30 mL, 48.04 mmol) over a period of 15 minutes. Stirring of the suspension at −50 to −60° C. for 30 minutes resulted in a color change to yellow, after which a solution of freshly fused ZnCl2 (98%; 3.49 g, 25.11 mmol) in dry THF (25 mL) was added dropwise at −50° C. to −60° C. over a period of 20 minutes. The reaction mixture was then stirred at −55° C. for 1 hour, the suspension is cooled to −78° C. and intermediate (7), (5.74 g, 11.49 mmol) in dry THF (10 mL) was added dropwise over a period of 30 minutes. The reaction mixture was stirred at −78° C. for 1 hour and then allowed to warm up to −40° C. over a period of 4 hours. After stirring at room temperature for 20 minutes, the mixture was poured into a saturated NH4Cl solution containing 10% of NH4OH (200 mL). The solution was stirred an additional 30 minutes then the aqueous layer was extracted with n-hexane/diethyl ether 95:5 (4×100 mL). The combined organic layers were dried over anhydrous MgSO4, the solvent removed under reduced pressure and the crude residue was purified over silica (n-hexane) to afford 3.96 g (79% yield) of the desired intermediate (8) as a colorless oil which was characterized as follows:

Workup

  1. additionwas added dropwise at −50° C. to −60° C. over a period of 20 minutes
  2. temperaturethe suspension is cooled to −78° C.
  3. stirringThe reaction mixture was stirred at −78° C. for 1 hour
  4. temperatureto warm up to −40° C. over a period of 4 hours
  5. stirringAfter stirring at room temperature for 20 minutes
  6. stirringThe solution was stirred an additional 30 minutes
  7. extractionthe aqueous layer was extracted with n-hexane/diethyl ether 95:5 (4×100 mL)
  8. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  9. customthe solvent removed under reduced pressure
  10. customthe crude residue was purified over silica (n-hexane)

Sources & evidence

ORD record
ord-aaede1cc0e9a467fbe6dc38583f202a5
Source dataset
uspto-grants-2010_04
Patent number
US07704986B2

Reaction notes

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