Water → Tafluprost

HRID 517393Notes

Reaction equation

HRID 517393 reaction equation
[CH2:1]1[C@@H:5]([OH:6])[C@H:4](/[CH:7]=[CH:8]/[C:9]([F:19])([F:18])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@@H:3]([CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C@H:2]1[OH:29].C([O-])([O-])=O.[K+].[K+].I[CH:37]([CH3:39])[CH3:38].O>CN(C=O)C.C(OCC)(=O)C>[CH3:38][CH:37]([O:27][C:26]([CH2:25][CH2:24][CH2:23]/[CH:22]=[CH:21]\[CH2:20][C@@H:3]1[C@@H:4](/[CH:7]=[CH:8]/[C:9]([F:18])([F:19])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:5]([OH:6])[CH2:1][C@@H:2]1[OH:29])=[O:28])[CH3:39]

Participants

7

Reactant 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 9978917209860-88-8

Product 1

HCID 9868491Tafluprost

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A sample of this product was hydrolyzed using methanol and 3N NaOH. After 2 h at 25° C., the mixture was acidified and extracted with ethyl acetate. After drying-concentration of the extracts, crude 11-protected Tafluprost acid was obtained. The crude 11-protected Tafluprost acid was esterified using K2CO3 and 2-iodopropane in DMF. After 2 h at 60° C., water and ethyl acetate were added and phase separated, the aqueous layer was extracted with ethyl acetate. After drying-concentration of the extracts, crude 11-protected Tafluprost was obtained. The crude 11-protected Tafluprost was deprotected using 3N HCl in THF and water. After 1 h at 25° C., saturated aqueous solution of sodium bicarbonate was added and phase separated, the aqueous layer was extracted with ethyl acetate. After drying-concentration of the extracts, crude Tafluprost was obtained. HPLC (Phenomenex Luna 5 μm silica) analysis of the crude product showed that 0.4% 5,6-trans isomer was found and HPLC (Chiralcel OD-H) analysis of the crude product showed that 0.1% enantiomer was found.

Workup

  1. customphase separated
  2. extractionthe aqueous layer was extracted with ethyl acetate

Sources & evidence

ORD record
ord-95b9b81e5c064e85a091dbee47ae0eb0
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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