Water → Acetic acid, (((2S,3R,4E,6E,8Z,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxy-4,6,8,10-tridecatetraenyl)oxy)-, methyl ester

HRID 1671744Notes

Reaction equation

HRID 1671744 reaction equation
[Zn:1].[F:2][C:3]1[CH:31]=[CH:30][C:6]([O:7][CH2:8][C@@H:9]([OH:29])/[CH:10]=[CH:11]/[C:12]#[C:13]/[CH:14]=[CH:15]/[CH:16]=[CH:17]/[C@@H:18]([OH:28])[C@@H:19]([OH:27])[CH2:20][O:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[CH:5][CH:4]=1.O>CO>[Zn:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([O:7][CH2:8][C@@H:9]([OH:29])/[CH:10]=[CH:11]/[CH:12]=[CH:13]\[CH:14]=[CH:15]\[CH:16]=[CH:17]\[C@@H:18]([OH:28])[C@@H:19]([OH:27])[CH2:20][O:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 962WaterHCID 23994Zinc2×HCID 9823441Acetic acid, (((2S,3R,4E,6E,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxy-4,6,10-tridecatrien-8-ynyl)oxy)-, methyl ester

Product 2

HCID 23994ZincHCID 10112981Acetic acid, (((2S,3R,4E,6E,8Z,10E,12S)-13-(4-fluorophenoxy)-2,3,12-trihydroxy-4,6,8,10-tridecatetraenyl)oxy)-, methyl esterYield 10.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Activated zinc was prepared from 10 g of zinc and the reduction carried out using the procedure described in Helv. Chim. Acta (1987), Vol. 70, p. 1025). A solution of (5S,6R,7E,9E,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-3-oxahexadeca-7,9,13-trien-11-ynoic acid, methyl ester, (0.8 g, 1.2 mmol) in methanol (4 mL) was added to a slurry of activated zinc in 1:1 methanol:water (45 mL). The flask was stirred vigorously under nitrogen for 24-60 hours. The mixture was filtered through a pad of Celite 545 and rinsed with methanol (3x25 mL). Purification by chromatography on a reverse phase semi-prep column using a gradient of acetonitrile and water afforded 55 mg of (5S,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-3-oxa-7,9,11,13-hexadecatetraenoic acid, methyl ester, as an oil; 1H-NMR (400 mHz, methanol-d4) δ3.62 (m, 2H), 3.75 (s, 3H), 3.93 (m, 2H), 4.13 (m, 3H), 4.58 (m, 1H), 5.85 (m, 2H), 6.14 (m, 2H), 6.36 (m, 2H), 6.77 (m, 1H), 6.96 (m, 5H) ppm.

Workup

  1. filtrationThe mixture was filtered through a pad of Celite 545
  2. washrinsed with methanol (3x25 mL)
  3. customPurification by chromatography on a reverse phase semi-prep column

Sources & evidence

ORD record
ord-0c4e72ce3c6d4010a7a94b1415770ab4
Source dataset
uspto-grants-2011_08
Patent number
US07994346B2

Reaction notes

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