Chlorotrimethylsilane → HCID 71270603, compound

HRID 2406272Notes

Reaction equation

HRID 2406272 reaction equation
C(NCCC)CC.C([Li])CCC.CCCCCC.[CH2:19]([O:26][C@H:27]1[CH2:32][C@@H:31]2[C@@H:29]([O:30]2)[C@@H:28]1[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl[Si:43]([CH3:46])([CH3:45])[CH3:44]>COC(C)(C)C.C(OCC)(=O)C.CCCCCCC>[CH2:19]([O:26][C@H:27]1[CH2:32][C@@H:31]([O:30][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH:29]=[C:28]1[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 8058HexaneHCID 8902DipropylamineHCID 11077786(1S,2R,3S,5R)-3-(Benzyloxy)-2-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hexaneHCID 178418339Butyllithium

Product 1

HCID 71270603HCID 71270603, compoundYield 97.4%

Reagents, catalysts & solvents 2

HCID 15413tert-Butyl methyl etherSolvent2×HCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of dipropylamine (212 mL, 1.55 mol) in 2-methoxy-2-methylpropane (2000 mL) at −15° C. under a blanket of nitrogen, 2.50 M of n-butyllithium in hexane (567 mL, 1.42 mol) was added slowly over 10 minutes, maintaining a temperature of less than −10° C. The resulting white suspension was stirred for 30 minutes at −15° C. To this suspension was added (1S,2R,3S,5R)-3-(benzyloxy)-2-(benzyloxymethyl)-6-oxabicyclo[3.1.0]hexane (21) (400.00 g, 1.29 mol) slowly as a solution in methyl tert-butyl ether (1200 mL) over 30 minutes, maintaining an internal temperature of less than −10° C. The reaction mixture was stirred for 30 minutes at −15° C. TLC analysis indicated no remaining starting material (20% ethyl acetate/heptane). Chlorotrimethylsilane (204 mL, 1.61 mol) was added while maintaining a temperature of less than −10° C. The mixture was allowed to warm to 0° C. and stirred for 30 minutes. TLC analysis indicated that no alcohol intermediate (20% ethyl acetate/heptane). The reaction mixture was quenched with the slow addition of water (4 L) while maintaining an internal temperature of less than 8° C. The aqueous layer was separated and the organic layer was extracted 3 times with water (3×4 L) and once with saturated sodium chloride in water (4 L). The organic layer was concentrated under reduced pressure to give an orange oil (480 g, 97.4%) which was used without further purification. 1H NMR (300 MHz, CD3OD, δ): 7.18 (m, 10H), 5.65 (s, 1H), 4.55 (t, 1H), 4.30 (m, 5H), 4.02 (s, 2H), 2.58 (m, 1H), 1.47 (m, 1H) and 0.00 (s, 9H).

Workup

  1. temperaturemaintaining a temperature of less than −10° C
  2. temperaturemaintaining an internal temperature of less than −10° C
  3. stirringThe reaction mixture was stirred for 30 minutes at −15° C
  4. temperaturewhile maintaining a temperature of less than −10° C
  5. temperatureto warm to 0° C.
  6. stirringstirred for 30 minutes
  7. customThe reaction mixture was quenched with the slow addition of water (4 L)
  8. temperaturewhile maintaining an internal temperature of less than 8° C
  9. customThe aqueous layer was separated
  10. extractionthe organic layer was extracted 3 times with water (3×4 L)
  11. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-899589ef557b4eef817696e140811158
Source dataset
uspto-grants-2014_08
Patent number
US08809356B2

Reaction notes

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