Sodium hydride → 2-[4-(4-Cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-phenyl]-[1,3]dioxane

HRID 1828708Notes

Reaction equation

HRID 1828708 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([SH:13])=[CH:9][CH:8]=1.[H-].[Na+].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[C:20]([C:30]([F:33])([F:32])[F:31])[CH:19]=1.[NH4+].[Cl-]>CN(C=O)C>[CH:24]1([C:21]2[CH:22]=[CH:23][C:18]([CH2:17][S:13][C:10]3[CH:11]=[CH:12][C:7]([CH:2]4[O:3][CH2:4][CH2:5][CH2:6][O:1]4)=[CH:8][CH:9]=3)=[CH:19][C:20]=2[C:30]([F:31])([F:32])[F:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 220577404-[1,3]Dioxan-2-yl-benzenethiolHCID 220577494-(Bromomethyl)-1-cyclohexyl-2-(trifluoromethyl)benzene

Product 1

HCID 220577252-[4-(4-Cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-phenyl]-[1,3]dioxane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Crude 4-[1,3]dioxan-2-yl-benzenethiol (0.9 mmol) is dissolved in DMF (15 mL, anhydrous). The solution is cooled to 0° C. followed by addition of NaH (76 mg, 1.8 mmol). After stirring for 30 min, the 4-bromomethyl-1-cyclohexyl-2-trifluoromethyl-benzene prepared above (0.8 mmol) dissolved in DMF (2 mL) is added dropwise via syringe. The mixture is stirred for 1 h, then poured into a mixture of ice and saturated aqueous NH4Cl. The aqueous phase is extracted with diethyl ether (3×30 mL). The combined organic layers are washed with saturated aqueous NaCl, dried over Na2SO4, and concentrated. The residue obtained is purified by silica gel chromatography (10% ethyl acetate in hexanes) to give 2-[4-(4-cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-phenyl]-[1,3]dioxane as white solid.

Workup

  1. additionis added dropwise via syringe
  2. stirringThe mixture is stirred for 1 h
  3. extractionThe aqueous phase is extracted with diethyl ether (3×30 mL)
  4. washThe combined organic layers are washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customis purified by silica gel chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a5d950b9142a4cfab357ea932fe3eceb
Source dataset
uspto-grants-2006_06
Patent number
US07060697B2

Reaction notes

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