Sodium hydride → 2-Chloro-5-cyclopentyl-5-hydroxy-3-oxo-non-8-ynoic Acid Methyl Ester

HRID 1453326노트

반응식

HRID 1453326 반응식
[H-].[Na+].[CH3:3][O:4][C:5](=[O:11])[CH:6]([Cl:10])[C:7]([CH3:9])=[O:8].C([Li])CCC.[CH:17]1([C:22](=[O:27])[CH2:23][CH2:24][C:25]#[CH:26])[CH2:21][CH2:20][CH2:19][CH2:18]1>C1COCC1>[CH3:3][O:4][C:5](=[O:11])[CH:6]([Cl:10])[C:7](=[O:8])[CH2:9][C:22]([CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21]1)([OH:27])[CH2:23][CH2:24][C:25]#[CH:26]

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 107332Methyl 2-chloroacetoacetateHCID 224997991-Cyclopentyl-pent-4-yn-1-oneHCID 178418339Butyllithium

생성물 1

HCID 587622142-Chloro-5-cyclopentyl-5-hydroxy-3-oxo-non-8-ynoic Acid Methyl Ester수율 78.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A slurry of NaH (3.2 g, 60% suspension in mineral oil, 80 mmol) in dry THF (250 mL) was cooled to −40° C. Methyl-2-chloroacetoacetate (9.74 mL, 80 mmol) was added slowly. The reaction was stirred until all gas evolution had ceased, and then butyl lithium (2.5 M, 32 mL, 80 mmol) was added. The reaction was stirred for 10 minutes, and then 1-cyclopentyl-pent-4-yn-1-one (4.0 g, 27 mmol) from Step 2 above, was added as a solution in 20 mL THF. The reaction was stirred 1Hour, and then warmed to room temperature. The reaction was quenched with 1 N HCl (200 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 and the organic layers were combined. The organic layer was washed with water, and then concentrated by rotary evaporation. The crude product was purified by chromatography to yield the pure product (6.345 g, 78% yield). MS (ESI): 298 (M−H), 300 (M+2−H).

후처리

  1. stirringThe reaction was stirred for 10 minutes
  2. stirringThe reaction was stirred 1Hour
  3. customThe reaction was quenched with 1 N HCl (200 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with CH2Cl2
  6. washThe organic layer was washed with water
  7. concentrationconcentrated by rotary evaporation
  8. customThe crude product was purified by chromatography

출처 및 근거

ORD 기록
ord-28d72757337e481c8943d0f612ffe91f
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07473790B2

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