Tetrahydrofuran → 7-{(1r,4s,5r)-4-(Tert-butyl-dimethyl-silanyloxy)-5-[(e)-3-(tert-butyl-dimethyl-silanyloxy)-5-(3-chloro-benzo[b]thiophen-2-yl)-pent-1-enyl]-3,3-dimethyl-2-oxo-cyclopentyl}-hept-5-ynoic acid methyl ester

HRID 406806Notes

Reaction equation

HRID 406806 reaction equation
[C:1]([Si:5]([O:8][CH:9]([CH2:13][CH2:14][C:15]1[S:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[C:16]=1[Cl:24])/[CH:10]=[CH:11]/I)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[C:25]([Li])([CH3:28])([CH3:27])[CH3:26].C[Zn]C.[CH3:33][O:34][C:35](=[O:43])[CH2:36][CH2:37][CH2:38][C:39]#[C:40][CH2:41]I.[Cl-].[NH4+].[CH2:46]1[CH2:50][O:49][CH2:48][CH2:47]1>O>[CH3:33][O:34][C:35](=[O:43])[CH2:36][CH2:37][CH2:38][C:39]#[C:40][CH2:41][C@@H:46]1[C@@H:47](/[CH:11]=[CH:10]/[CH:9]([O:8][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:7])[CH3:6])[CH2:13][CH2:14][C:15]2[S:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[C:16]=2[Cl:24])[C@H:48]([O:8][Si:5]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:6])[CH3:1])[C:9]([CH3:13])([CH3:10])[C:50]1=[O:49]

Participants

8

Reactant 6

HCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 10901527Methyl 7-iodohept-5-ynoateHCID 21964438tert-Butyl-{(E)-1-[2-(3-chloro-benzo[b]thiophen-2-yl)-ethyl]-3-iodo-allyloxy}-dimethylsilaneHCID 178418306HCID 178418306, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 667609417-{(1r,4s,5r)-4-(Tert-butyl-dimethyl-silanyloxy)-5-[(e)-3-(tert-butyl-dimethyl-silanyloxy)-5-(3-chloro-benzo[b]thiophen-2-yl)-pent-1-enyl]-3,3-dimethyl-2-oxo-cyclopentyl}-hept-5-ynoic acid methyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A −78° C. solution of iodide 32 (675 mg, 1.34 mmol) in THF (2.0 mL) was treated with tert-butyllithium (1.73 mL, 2.94 mL, 1.7 M/pentane). The dark red mixture was stirred for 25 min. and then dimethylzinc (0.80 mL, 1.6 mmol, 2 M/toluene) was added. The solution was stirred at 0° C. for 15 min. and then recooled to −78° C. At this time, a solution of enone 6 (208 mg, 0.87 mmol) in THF (1.0 mL) was added over 2 h by syringe pump, rinsing with 0.5 mL THF. After 30 min., HMPA (1.34 mL, distilled from CaH2) was added followed by a solution of propargyl iodide 31 (1.286 g, 4.83 mmol) in THF (1.0 mL). The solution was stirred in a −40° C. bath overnight and then 20 mL saturated ammonium chloride solution and 10 mL water were added. The mixture was extracted with dichloromethane (20 mL) and ethyl acetate (2×20 mL). The combined organic extracts were dried (MgSO4), filtered and evaporated. Purification by flash chromatography on silica gel (5-10% ethyl acetate/hexanes) gave 198 mg (0.27 mmol, 31%) of 33.

Workup

  1. stirringThe solution was stirred at 0° C. for 15 min.
  2. customrecooled to −78° C
  3. washrinsing with 0.5 mL THF
  4. waitAfter 30 min.
  5. additionHMPA (1.34 mL, distilled from CaH2) was added
  6. stirringThe solution was stirred in a −40° C. bath overnight
  7. extractionThe mixture was extracted with dichloromethane (20 mL) and ethyl acetate (2×20 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customPurification by flash chromatography on silica gel (5-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-60c6a91639f84da18a227a098c95e618
Source dataset
uspto-grants-2014_06
Patent number
US08754122B2

Reaction notes

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