Isopropyl iodide → Latanoprost

HRID 1372375Notes

Reaction equation

HRID 1372375 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([CH2:7][CH2:8][C@H:9]([OH:28])[CH2:10][CH2:11][C@@H:12]2[C@@H:16]([CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[C@@H:15]([OH:26])[CH2:14][C@H:13]2[OH:27])=[CH:5][CH:6]=1.[CH:29](I)([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].OS([O-])(=O)=O.[Na+]>CCOCC.CN(C=O)C>[CH3:30][CH:29]([O:24][C:23]([CH2:22][CH2:21][CH2:20]/[CH:19]=[CH:18]\[CH2:17][C@@H:16]1[C@@H:12]([CH2:11][CH2:10][C@@H:9]([OH:28])[CH2:8][CH2:7][C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=2)[C@H:13]([OH:27])[CH2:14][C@@H:15]1[OH:26])=[O:25])[CH3:31]

Participants

7

Reactant 4

HCID 6362Isopropyl iodideHCID 10796Cesium carbonateHCID 516919Sodium BisulfateHCID 6441636Latanoprost acid

Product 1

HCID 5311221Latanoprost

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of Latanoprost acid (0.95 g, 2.4 mmol), isopropyl iodide (0.83 g, 4.8 mmol), cesium carbonate (1.20 g, 3.6 mmol) and DMF (20 mL) was stirred for 2–3 hours at 40–50° C. (TLC monitoring) and poured into a stirred mixture of 2 M aqueous NaHSO4 (2.5 mL, 5 mmol), ice (50 mL) and ether (50 mL). The organic layer was separated and the water phase was extracted with ether (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure to give 1.05 g (100% yield) of crude product. The crude product was purified by column chromatography on silica gel (hexane/ethyl acetate 1:1 v/v) to give Latanoprost. 1H NMR (CDCl3) is compatible with literature data.

Workup

  1. customThe organic layer was separated
  2. extractionthe water phase was extracted with ether (2×50 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give 1.05 g (100% yield) of crude product
  8. customThe crude product was purified by column chromatography on silica gel (hexane/ethyl acetate 1:1 v/v)

Sources & evidence

ORD record
ord-3c46e7627a064f339cd0183c7a0d79d1
Source dataset
uspto-grants-2007_01
Patent number
US07157590B2

Reaction notes

Loading…