Chlorotrimethylsilane → 2-Carbomethoxy-2-(t-butyl)thiomethyl-1,2,3,4-tetrahydronaphthalene

HRID 1656045

Reaction equation

HRID 1656045 reaction equation
C(N[CH:5]([CH3:7])[CH3:6])(C)C.C([Li])CCC.[C:13]([CH:17]1[CH2:26][CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1)([O:15][CH3:16])=[O:14].[CH3:27][Si](Cl)(C)C.C([CH:36]([S:38]C(Cl)C(C)(C)C)Cl)(C)(C)C>O1CCCC1.CCCCCC.[Br-].[Zn+2].[Br-]>[C:13]([C:17]1([CH2:36][S:38][C:5]([CH3:6])([CH3:7])[CH3:27])[CH2:26][CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1)([O:15][CH3:16])=[O:14]

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 12588372Methyl 1,2,3,4-tetrahydronaphthalene-2-carboxylateHCID 86747282t-Butyl chloromethylsulfideHCID 178418339Butyllithium

Product 1

HCID 197899492-Carbomethoxy-2-(t-butyl)thiomethyl-1,2,3,4-tetrahydronaphthaleneYield 65.9%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

Dissolve diisopropylamine (2.31 mL, 16.5 mmol) in anhydrous tetrahydrofuran (10 mL), cool to -70° C. and place under an argon atmosphere. Add, by dropwise addition, n-butyllithium (6.6 mL of a 2.5M solution in hexane, 16.5 mmol). Stir at -70° C. for 20 minutes then add, by dropwise addition, a solution of 2-carbomethoxy-1,2,3,4-tetrahydronaphthalene (2.85 g, 15 mmol) in anhydrous tetrahydrofuran (10 mL). Stir an additional 30 minutes then add trimethylsilyl chloride (1.9 mL, 15 mmol). Evaporate the solvent in vacuo and suspend the residue in anhydrous methylene chloride (30 mL). Treat with t-butyl chloromethylsulfide (2.08 g, 15 mmol) and 3 portions of zinc bromide (300 mg each) over 15 minutes. The mixture spontaneously warms to reflux. Quickly bring to room temperature with an ice bath and wash with water then saturated sodium hydrogen carbonate. Dry (MgSO4) and evaporate the solvent in vacuo to give a yellow oil. Purify by silica gel chromatography (30% methylene chloride/hexane then 70% methylene chloride/hexane) and recrystallize (methanol) to give the title compound (2.89 g, 65.2%).

Workup

  1. additionthen add, by dropwise addition
  2. stirringStir an additional 30 minutes
  3. customEvaporate the solvent in vacuo
  4. temperatureto reflux
  5. customQuickly bring to room temperature with an ice bath
  6. washwash with water
  7. dry with materialDry (MgSO4)
  8. customevaporate the solvent in vacuo
  9. customto give a yellow oil
  10. customPurify by silica gel chromatography (30% methylene chloride/hexane
  11. custom70% methylene chloride/hexane) and recrystallize (methanol)

Sources & evidence

ORD record
ord-96dd8943b1f14d52a4df5abe5836c991
Source dataset
uspto-grants-1993_10
Patent number
US05252601

Linked notes

Loading…