Water → Tafluprost

HRID 517398Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 80 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-a021b61958014e478aa974248c4a0ba5
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115109B2

Reaction notes

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