Isopropyl iodide → Latanoprost

HRID 584887Notes

Reaction equation

HRID 584887 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

Conditions

Temperature
45 °C

Procedure

A mixture of Latanoprost acid [13b] (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. (TMC 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-f09f2a45ceff435d9aa29ce707cc14b1
Source dataset
uspto-grants-2005_08
Patent number
US06927300B2

Reaction notes

Loading…