HCID 59431063, compound → HCID 131732771, compound

HRID 1474609Notes

Reaction equation

HRID 1474609 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:23])=[C:6]([CH:22]=1)[CH2:7][C:8]1[CH:21]=[CH:20][C:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[CH:10][CH:9]=1.[Li]CCCC.[Si:29]([O:36][C@H:37]1[C@H:44]2[C@H:40]([O:41][C:42]([CH3:46])([CH3:45])[O:43]2)[O:39][C@H:38]1[CH:47]=[O:48])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C1COCC1>[Si:29]([O:36][C@H:37]1[C@H:44]2[C@H:40]([O:41][C:42]([CH3:46])([CH3:45])[O:43]2)[O:39][C@H:38]1[CH:47]([C:2]1[CH:3]=[CH:4][C:5]([Cl:23])=[C:6]([CH2:7][C:8]2[CH:21]=[CH:20][C:11]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[CH:10][CH:9]=2)[CH:22]=1)[OH:48])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:30])[CH3:31]

Participants

5

Reactant 3

HCID 59431063HCID 59431063, compoundHCID 59747702(4-(5-Bromo-2-chlorobenzyl)phenoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 131732771HCID 131732771, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of (4-(5-bromo-2-chlorobenzyl)phenoxy)(tert-butyl)dimethylsilane (14.2 g, 34.57 mmol, prepared following the procedure given in US20070049537) in dry THF (90 mL) was cooled to −78° C. and nBuLi (30.7 mL, 46.05 mmol, 1.5 M solution in hexane) was added drop wise while stirring and stirring was continued for further 30 min. A solution of (3aS,5R,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde (7.0 g, 23.05 mmol, prepared according to the procedure given in NUCLEOSIDE, NUCLOETIDES & NUCLEIC ACIDS, 20(4-7), 649-652 (2001)) in dry THF (13 mL) was added dropwise to the reaction mixture and stirred at the same temperature for 2 h. Reaction temperature was raised slowly to 0° C. and then stirred at r.t. for 16 h. After completion of reaction, as confirmed by TLC, reaction mixture was quenched by the addition of saturated NH4Cl solution and extracted with ethyl acetate (3×300 mL). The combined organic layers were dried over Na2SO4 and the volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 0.2:9.8 Acetone:Pet. Ether) to afford the title compound (3.66 g, 25%)

Workup

  1. stirringstirring
  2. stirringstirred at the same temperature for 2 h
  3. customReaction temperature
  4. temperaturewas raised slowly to 0° C.
  5. stirringstirred at r.t. for 16 h
  6. customAfter completion of reaction
  7. customas confirmed by TLC, reaction mixture
  8. customwas quenched by the addition of saturated NH4Cl solution
  9. extractionextracted with ethyl acetate (3×300 mL)
  10. dry with materialThe combined organic layers were dried over Na2SO4
  11. customthe volatiles were evaporated in vacuo
  12. customThe residue obtained
  13. customwas purified by column chromatography (silica gel, 0.2:9.8 Acetone:Pet. Ether)

Sources & evidence

ORD record
ord-a570a5f858ed4af1848df345e1d933b8
Source dataset
uspto-grants-2015_04
Patent number
US09018249B2

Reaction notes

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