Hexane → Tert-butyl{[3-(methylsulfinyl)-3-(methylthio)cyclobutyl]oxy}diphenylsilane

HRID 717864Notes

Reaction equation

HRID 717864 reaction equation
[CH3:1][S:2]([CH2:4][S:5][CH3:6])=[O:3].C([Li])CCC.CCCCCC.Br[CH2:19][CH:20]([CH2:39]Br)[O:21][Si:22]([C:35]([CH3:38])([CH3:37])[CH3:36])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O1CCCC1.O>[C:35]([Si:22]([O:21][CH:20]1[CH2:39][C:4]([S:2]([CH3:1])=[O:3])([S:5][CH3:6])[CH2:19]1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 8058HexaneHCID 99129Methyl (methylsulfinyl)methyl sulfideHCID 69673452[2-Bromo-1-(bromomethyl)ethoxy](tert-butyl)diphenylsilaneHCID 178418339Butyllithium

Product 1

HCID 86666495Tert-butyl{[3-(methylsulfinyl)-3-(methylthio)cyclobutyl]oxy}diphenylsilane

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of (methylsulfinyl)(methylthio)methane (27.70 g, 223.0 mmol) in tetrahydrofuran (90 mL) at −10° C. was added dropwise, a solution of 2.5 M n-butyllithium in hexane (89.2 mL, 223 mmol). The mixture was stirred at −10° C. for 2 hours. It was then cooled to −78° C. and transferred by cannula in a slow manner to a solution of [2-bromo-1-(bromomethyl)ethoxy](tert-butyl)diphenylsilane (42 g, 93 mmol, from Step 1) in tetrahydrofuran (70 mL, 900 mmol) held at −78° C. The mixture was stirred with warming to room temperature over 2 nights. Water was added, and then the product was extracted with three portions of DCM. The combined extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography (eluting with a gradient from 0-100% ethyl acetate/hexanes) afforded desired product as a mixture of diastereomers (34.1 g, 88%). 1H NMR (300 MHz, CDCl3), diastereomers: δ 7.74-7.58 (m, 8H), 7.48-7.31 (m, 10H), 4.52 (tt, 1H), 4.42 (tt, 1H), 3.05-1.99 (m, 8H), 2.47 (s, 3H), 2.42 (s, 3H), 2.13 (s, 3H), 2.00 (s, 3H), 1.05 (s, 9H), 1.02 (s, 9H).

Workup

  1. temperatureIt was then cooled to −78° C.
  2. customheld at −78° C
  3. stirringThe mixture was stirred
  4. temperaturewith warming to room temperature over 2 nights
  5. extractionthe product was extracted with three portions of DCM
  6. dry with materialThe combined extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography (eluting with a gradient from 0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-eb95b3ec3a564118b1b75b628ef38df7
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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