Methanol → 5-(3-((1R,2R,3R,5R)-5-chloro-2-((3S,7R,E)-3,7-dihydroxyoct-1-enyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic Acid

HRID 1037726Notes

Reaction equation

HRID 1037726 reaction equation
[Cl:1][C@H:2]1[C@H:6]([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([C:15]([O:17]C)=[O:16])=[CH:12][CH:11]=2)[C@@H:5](/[CH:19]=[CH:20]/[C@@H:21]([OH:28])[CH2:22][CH2:23][CH2:24][C@H:25]([OH:27])[CH3:26])[C@H:4]([OH:29])[CH2:3]1.[OH-].[Li+].CO.S([O-])(O)(=O)=O.[Na+]>C1COCC1>[Cl:1][C@H:2]1[C@H:6]([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([C:15]([OH:17])=[O:16])=[CH:12][CH:11]=2)[C@@H:5](/[CH:19]=[CH:20]/[C@@H:21]([OH:28])[CH2:22][CH2:23][CH2:24][C@H:25]([OH:27])[CH3:26])[C@H:4]([OH:29])[CH2:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 516919Sodium BisulfateHCID 57734135Methyl 5-(3-((1R,2R,3R,5R)-5-chloro-2-((3S,7R,E)-3,7-dihydroxyoct-1-enyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylate

Product 1

HCID 577341035-(3-((1R,2R,3R,5R)-5-chloro-2-((3S,7R,E)-3,7-dihydroxyoct-1-enyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic AcidYield 58.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 76 mg of ester 11 (0.17 mmol) in 1 mL of THF was hydrolyzed with 360 uL of aqueous lithium hydroxide (0.5M, 0.18 mmol)) and 0.2 mL of methanol at 24° C. for 6 h. The mixture was acidified by addition of solid sodium hydrogen sulfate (25 mg, 0.18 mmol) and the residual water was removed in vacuo. The residual solid was extracted with ethyl acetate and the product acid was purified by PLC on a 0.5 mm thick preparative silica gel plate eluted in 10% methanol:90% ethyl acetate. Extraction of the UV-active band yielded 43 mg of free acid 12 as an oil (54% yield); 1H NMR (CD3OD): 1.13 (d, J=6.3 Hz, 3H), 1.28-1.63 (m, 8H), 1.75-2.21 (m, 6H), 2.86 (t, J=7 Hz, 2H), 3.70 (m, 1H), 4.04 (m, 3H), 5.52 (m, 2H), 6.86 (br s, 1H), 7.58 (br s, 1H). HPLC purity was 100 A %. LCMS (ESI: M+-H20): 413.2.

Workup

  1. customat 24° C.
  2. customfor 6 h
  3. customthe residual water was removed in vacuo
  4. extractionThe residual solid was extracted with ethyl acetate
  5. customthe product acid was purified by PLC on a 0.5 mm thick preparative silica gel plate
  6. washeluted in 10% methanol
  7. extractionExtraction of the UV-active band

Sources & evidence

ORD record
ord-7414a7bc4c984a05b3f7c18f848aedd2
Source dataset
uspto-grants-2013_10
Patent number
US08546603B2

Reaction notes

Loading…