(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-on → HCID 59235394, compound

HRID 2174341Notes

Reaction equation

HRID 2174341 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][O:19][CH2:20][CH:21]([F:23])[F:22])=[CH:12][CH:11]=2)[CH:3]=1.[CH2:24]([Li])CCC.C[Si](C)(C)[O:31][C@@H:32]1[C@@H:37]([O:38][Si](C)(C)C)[C@H:36]([O:43][Si](C)(C)C)[C@@H:35]([CH2:48][O:49][Si](C)(C)C)[O:34][C:33]1=[O:54]>C1COCC1.C1(C)C=CC=CC=1.CCCCCC.C1(C)C=CC=CC=1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:33]2([O:54][CH3:24])[C@H:32]([OH:31])[C@@H:37]([OH:38])[C@H:36]([OH:43])[C@@H:35]([CH2:48][OH:49])[O:34]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][O:19][CH2:20][CH:21]([F:23])[F:22])=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 59235327HCID 59235327, compoundHCID 178418339Butyllithium

Product 1

HCID 59235394HCID 59235394, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-60 °C

Procedure

To a cold (−60° C.) solution of 4-bromo-1-chloro-2-(4-(2-(2,2-difluoroethoxy)ethoxy)benzyl)benzene (4 g, 9.9 mmol) in dry THF/toluene (2:1, 18 mL) was slowly added dropwise a solution of n-butyllithium in hexane (2.5 M, 4.7 mL), and the pale yellow solution was stirred for 30 minutes at −60° C. A solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (6 g, 12.8 mmol) in toluene (15 mL) was added dropwise at a rate that maintained the temperature below −55° C., and the mixture was stirred for 2 hr at −60° C. The reaction mixture was quenched by addition of MeOH (24 mL) containing methanesulfonic acid (2 mL). The reaction was stirred overnight at RT, and then aqueous sodium hydrogen carbonate solution (30 mL) was added. The organic layer was separated, the aqueous phase was extracted with ethyl acetate (30 mL) and the combined organic extracts were dried over sodium sulfate. The product was concentrated to give a residue (5.4 g), which was used in the next step without further purification.

Workup

  1. temperaturethat maintained the temperature below −55° C.
  2. stirringthe mixture was stirred for 2 hr at −60° C
  3. customThe reaction mixture was quenched by addition of MeOH (24 mL)
  4. additioncontaining methanesulfonic acid (2 mL)
  5. stirringThe reaction was stirred overnight at RT
  6. additionaqueous sodium hydrogen carbonate solution (30 mL) was added
  7. customThe organic layer was separated
  8. extractionthe aqueous phase was extracted with ethyl acetate (30 mL)
  9. dry with materialthe combined organic extracts were dried over sodium sulfate
  10. concentrationThe product was concentrated

Sources & evidence

ORD record
ord-1b722f91e8f34551814e24086c129155
Source dataset
uspto-grants-2015_06
Patent number
US09061060B2

Reaction notes

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