Sodium hydride → (1S,5S)-3-Benzenesulfonyl-1-(1-naphthyl)-3-methylsulfanyl-bicyclo[3.1.0]hexane

HRID 1096758Notes

Reaction equation

HRID 1096758 reaction equation
[CH3:1][S:2][CH2:3][S:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:6])=[O:5].[H-].[Na+].Br[CH2:16][C@@:17]1([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][CH:23]=2)[CH2:19][CH:18]1[CH2:20]Br.C(OCC)(=O)C.CCCCCC>CN(C)C=O>[C:7]1([S:4]([C:3]2([S:2][CH3:1])[CH2:20][C@H:18]3[C@:17]([C:22]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[CH:25]=[CH:24][CH:23]=4)([CH2:19]3)[CH2:16]2)(=[O:5])=[O:6])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 643313Methylthiomethyl phenyl sulfoneHCID 21226206Ethyl acetate hexaneHCID 59779128(1S)-1,2-bis(bromomethyl)-1-(1-naphthyl)cyclopropane

Product 1

HCID 86622518(1S,5S)-3-Benzenesulfonyl-1-(1-naphthyl)-3-methylsulfanyl-bicyclo[3.1.0]hexaneYield 145.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

1-((Methylthio)methylsulfonyl)benzene (6.54 g, 32.2 mmole) was dissolved in dry dimethylforamide (DMF, 40 mL). Sodium hydride (3.86 g, 80.5 mmol) was added portion wise under nitrogen atmosphere at 0° C. The reaction mass was gradually heated to 40° C. and maintained for 30 minutes at 40° C. (1S)-1,2-bis(bromomethyl)-1-(1-naphthyl)cyclopropane (5.7 g, 6.1 mmol) dissolved in DMF (15 mL) was added dropwise for 30 min at 0° C. The temperature of the reaction mass was gradually brought to room temperature and maintained for 7 hours. The reaction was monitored by TLC (ethyl acetate/hexane (10:90)). The reaction mass was quenched with water. The aqueous layer was extracted with diethyl ether (2×250 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to yield 12.0 g of crude oil that was purified by column chromatography (silica gel, ethyl acetate/hexane (4:96) to yield 3.5 g (53%) of product. 1H NMR δ(300 MHz,CDCl3): 1.93 (2H,m), 2.01 (1H,m), 2.07 (3H,s), 2.28 (2H,m), 2.44 (2H,m), 2.88 (1H, dd, J=15 Hz), 7.36 (1H,m), 7.47-7.68 (7H,m), 7.74 (1H,m), 7.91-7.97 (3H,m).

Workup

  1. additionwas added dropwise for 30 min at 0° C
  2. customwas gradually brought to room temperature
  3. temperaturemaintained for 7 hours
  4. customThe reaction mass was quenched with water
  5. extractionThe aqueous layer was extracted with diethyl ether (2×250 mL)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto yield 12.0 g of crude oil that
  10. customwas purified by column chromatography (silica gel, ethyl acetate/hexane (4:96)

Sources & evidence

ORD record
ord-2d1c4100ad934f438f3a45d6d09b9b86
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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