Water → Travoprost

HRID 517374

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HRID 517374 반응식
[OH:1][C@@H:2]1[CH2:6][C@H:5]([OH:7])[C@H:4]([CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])[C@H:3]1/[CH:17]=[CH:18]/[C@@H:19]([OH:32])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.C([O-])([O-])=O.[K+].[K+].I[CH:40]([CH3:42])[CH3:41].O>CN(C=O)C.C(OCC)(=O)C>[OH:1][C@@H:2]1[CH2:6][C@H:5]([OH:7])[C@H:4]([CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][C:14]([O:16][CH:40]([CH3:42])[CH3:41])=[O:15])[C@H:3]1/[CH:17]=[CH:18]/[C@@H:19]([OH:32])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:29])([F:30])[F:31])[CH:23]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 5311100Fluprostenol

생성물 1

HCID 5282226Travoprost수율 99.9%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

A solution of crude Travoprost acid (1.1 g from Example 9) in DMF (11 mL) was treated with K2CO3 (0.90 g, 6.5 mmol) and 2-iodopropane (0.74 g, 4.4 mmol). This mixture was then stirred at 80° C. for 2 hr under an atmosphere of nitrogen (TLC monitoring). Water (30 mL) and ethyl acetate (30 mL) were added and the mixture was stirred for 10 min. The aqueous layer was separated and extracted with ethyl acetate (30 mL), and the combined organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give 1.2 g of crude Travoprost. The crude Travoprost was dissolved in 10 mL ethyl acetate in 25 mL round-bottom flask, followed by addition of imidazole (0.82 g, 12 mmol) at room temperature. Chlorotriethylsiliane (1.6 g, 10.6 mmol) was added into this flask and stirred for 10 minutes. White solid was produced and filtered off and washed with 50 mL ethyl acetate twice. All organic solvent was combined and washed with 15 mL saturated NaHCO3 aqueous solution twice. The organic layer was dried over anhydrous MgSO4, solid was filtered off and solvent was evaporated under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. Yield of the title compound was 1.85 g. (91.6%)

후처리

  1. stirringthe mixture was stirred for 10 min
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (30 mL)
  4. dry with materialthe combined organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-39d6aa0d14dd41a6a03e91df47884f46
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115109B2

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