Sodium hydride → 3-Triisopropylsilanyloxy-1-vinyl-cyclopentanecarboxylic acid

HRID 2176325Notes

Reaction equation

HRID 2176325 reaction equation
[H-].[Na+].C([O:5][C:6]([C:8]1([CH:24](O)[CH3:25])[CH2:12][CH2:11][CH:10]([O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH2:9]1)=[O:7])C.C1C(Cl)=CN=C(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)C=1>O1CCCC1>[CH:21]([Si:14]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[O:13][CH:10]1[CH2:11][CH2:12][C:8]([CH:24]=[CH2:25])([C:6]([OH:7])=[O:5])[CH2:9]1)([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 388544N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-trifluoromethanesulfonylmethanesulfonamideHCID 867061731-(1-Hydroxy-ethyl)-3-triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl ester

Product 1

HCID 867061743-Triisopropylsilanyloxy-1-vinyl-cyclopentanecarboxylic acidYield 15.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A cooled (−78° C.) suspension of sodium hydride (1.474 g, 36.868 mmol, 60% dispersed in mineral oil) in anhydrous tetrahydrofuran (60 mL) was treated with a solution of 1-(1-hydroxy-ethyl)-3-triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl ester (6.61 g, 18.434 mmol). After stirring at −78° C. for 10 min, the reaction mixture was treated with a solution of N-(5-chloro-2-pyridyl)bis(trifluoromethanesulfonimide) (13.2 g, 33.615 mmol) in anhydrous tetrahydrofuran (20 mL). The cooling bath was removed and the reaction was allowed to stir at room temperature for 24 h. More sodium hydride (1.474 g, 36.868 mmol, 60% dispersed in mineral oil) was added. After stirring at room temperature for 5 h, more sodium hydride (1.474 g, 36.868 mmol, 60% dispersed in mineral oil) was added. After stirring at room temperature for 17.5 h, the reaction was quenched at 0° C. with a saturated solution of ammonium chloride (100 mL). The aqueous layer was extracted with dichloromethane (2×). The aqueous layer was acidified to pH 2 with hydrochloric acid (2 M) and extracted with dichloromethane. The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 followed by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 4:1 to afford the title compound (876.9 mg, 15%) as a light yellow oil and as a 3:1 mixture of diastereoisomers. LCMS (m/z) 311.2 [M−H], Tr=4.05 min.

Workup

  1. temperatureA cooled
  2. customThe cooling bath was removed
  3. stirringto stir at room temperature for 24 h
  4. stirringAfter stirring at room temperature for 5 h
  5. stirringAfter stirring at room temperature for 17.5 h
  6. customthe reaction was quenched at 0° C. with a saturated solution of ammonium chloride (100 mL)
  7. extractionThe aqueous layer was extracted with dichloromethane (2×)
  8. extractionextracted with dichloromethane
  9. filtrationfiltered through a phase separator
  10. customthe volatiles were removed in vacuo
  11. customThe residue was purified by silica gel chromatography
  12. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1
  13. washeluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 4:1

Sources & evidence

ORD record
ord-db0825659e9140ebbcaf45a0fbd6b370
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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