Methyl iodide → Bimatoprost acid methyl ester

HRID 517408Notes

Reaction equation

HRID 517408 reaction equation
[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:28])[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[C:29](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[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][CH3:29])=[O:15])[C@H:3]1/[CH:17]=[CH:18]/[C@@H:19]([OH:28])[CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 5283081Bimatoprost Acid

Product 1

HCID 29935774Bimatoprost acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A solution of (5Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((S,E)-3-hydroxy-5-phenylpent-1-enyl)cyclopentyl)hept-5-enoic acid (2 g from Example 53) was dissolved in 20 ml N,N-dimethylformamide in 50 mL round-bottom flask, followed by addition of potassium carbonate (2.2 g, 16.2 mmol) and iodomethane (1.1 g, 8.1 mmol). The reaction mixture was heated to 40° C. and stirred for 2 hours. The mixture was cooled to room temperature and the solid was filtered off. The filtrate was subsequently diluted and extracted with 20 ml ethyl acetate and 20 ml water. The mixture was phase separated and the organic layer was dried over anhydrous MgSO4, the solid was filtered off and organic solvent was evaporated off 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 1.6 g (73.5% in 2 steps)

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationthe solid was filtered off
  3. additionThe filtrate was subsequently diluted
  4. extractionextracted with 20 ml ethyl acetate and 20 ml water
  5. customseparated
  6. dry with materialthe organic layer was dried over anhydrous MgSO4
  7. filtrationthe solid was filtered off
  8. customorganic solvent was evaporated off under vacuum
  9. customThe crude product was purified by chromatography on silica gel using
  10. additiona mixture of hexane and ethyl acetate as a gradient eluent

Sources & evidence

ORD record
ord-8b652eda24664b7d840e9d64d55c1c87
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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