Lithium Hexamethyldisilazide → (Rs)-(e)-methyl 4-[3-(4,4-dimethyl-thiochroman-6-yl)-oct-1-enyl]-benzoate

HRID 394936Notes

Reaction equation

HRID 394936 reaction equation
C(OP([CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1)(OCC)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:30][C:31]1([CH3:49])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH:42]=O)[CH:39]=2)[S:34][CH2:33][CH2:32]1>C1COCC1.CCCCCC>[CH3:49][C:31]1([CH3:30])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])/[CH:42]=[CH:9]/[C:10]3[CH:11]=[CH:12][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:18][CH:19]=3)[CH:39]=2)[S:34][CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 10946061Methyl 4-(diethoxyphosphorylmethyl)benzoateHCID 18177929(Rs)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal

Product 1

HCID 18177895(Rs)-(e)-methyl 4-[3-(4,4-dimethyl-thiochroman-6-yl)-oct-1-enyl]-benzoateYield 39.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

0.51 g of methyl 4-(diethoxyphosphorylmethyl)-benzoate were dissolved in 7.5 ml THF and treated, at −20° C., with 1.8 ml of a 1M solution of lithium bis(trimethylsilyl)amide in hexane. After 15 min. at −20° C., a solution of 350 mg of (RS)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal in 7.5 ml THF was added. The reaction mixture was stirred at room temperature for 1.5 hour. The mixture quenched by the addition of 10 ml of water and the resulting mixture was partitioned in 25 ml ethyl acetate/15 ml sat. aq. sodium chloride solution. The phases were separated and the organic phase was dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by flash chromatography (SiO2, 10% ethyl acetate/hexanes), giving 200 mg of the corresponding ester. 1H NMR (CDCl3): 7.94 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H), 7.19 (d, J=1.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.45 (d, J=15.9 Hz, 1H), 6.38 (d, J=15.9 Hz, 1H), 3.90 (s, 3H), 3.30 (m, 1H), 3.05-3.00 (m, 2H), 2.00-1.90 (m, 2H), 1.85-1.75 (m, 2H), 1.33 (s, 6H), 1.40-1.30 (m, 6H), 0.86 (t, J=6.5 HZ, 3H).

Workup

  1. customThe mixture quenched by the addition of 10 ml of water
  2. customthe resulting mixture was partitioned in 25 ml ethyl acetate/15 ml sat. aq. sodium chloride solution
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customthe crude product was purified by flash chromatography (SiO2, 10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-04d83852e5c84492861cf468980d9cbf
Source dataset
uspto-grants-2003_08
Patent number
US06603012B2

Reaction notes

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