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

HRID 2176325ノート

反応式

HRID 2176325 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

HCID 867061743-Triisopropylsilanyloxy-1-vinyl-cyclopentanecarboxylic acid収率 15.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-db0825659e9140ebbcaf45a0fbd6b370
出典データセット
uspto-grants-2015_06
特許番号
US09062092B2

反応ノート

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