Water → Tafluprost

HRID 517398노트

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HRID 517398 반응식
[F:1][C:2]([F:29])([CH2:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)/[CH:3]=[CH:4]/[C@H:5]1[C@H:9]([OH:10])[CH2:8][C@H:7]([OH:11])[C@@H:6]1[CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19].C([O-])([O-])=O.[K+].[K+].I[CH:37]([CH3:39])[CH3:38].O>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:29])([CH2:21][O:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)/[CH:3]=[CH:4]/[C@H:5]1[C@H:9]([OH:10])[CH2:8][C@H:7]([OH:11])[C@@H:6]1[CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][C:18]([O:20][CH:37]([CH3:39])[CH3:38])=[O:19]

참가 물질

7

반응물 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 9978917Tafluprost acid

생성물 1

HCID 9868491Tafluprost수율 105.8%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

A solution of crude Tafluprost acid (12.0 g from Example 36) in DMF (100 mL) was treated with K2CO3 (21.1 g, 0.12 mol.) and 2-iodopropane (11.4 g, 0.08 mol.). This mixture was then stirred at 80° C. for 2 hr under an atmosphere of nitrogen (TLC monitoring). Water (100 mL) and ethyl acetate (100 mL) was added and the mixture was stirred for 10 min. The aqueous layer was separated and extracted with ethyl acetate (100 mL), the combined organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give 14.0 g of crude Tafluprost. The crude Tafluprost was purified by column chromatography and then concentrated under reduced pressure to provide 6.8 g of Tafluprost (86% yield, 2 steps). HPLC (Phenomenex Luna 5 μm silica) analysis of the crude product showed that no isomer was detectable, and HPLC (Chiralcel OD-H) analysis of the crude product showed that no enantiomer was detectable.

후처리

  1. stirringthe mixture was stirred for 10 min
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (100 mL)
  4. dry with materialthe combined organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-a021b61958014e478aa974248c4a0ba5
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115109B2

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