Diethylamine → 2-[[(4S,5R)-5-[(1E,3E,7E,9S)-9-hydroxy-10-(4-fluorophenoxy)-1,3,7-decatrien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester

HRID 2078506Notes

Reaction equation

HRID 2078506 reaction equation
Br/[CH:2]=[CH:3]/[C@H:4]([OH:14])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.C(NCC)C.[CH:20](/[C@H:26]1[O:30][C:29]([CH3:32])([CH3:31])[O:28][C@H:27]1[CH2:33][O:34][CH2:35][C:36]([O:38][CH3:39])=[O:37])=[CH:21]\[CH:22]=[CH:23]\[C:24]#[CH:25]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[OH:14][C@H:4]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)/[CH:3]=[CH:2]/[C:25]#[C:24]/[CH:23]=[CH:22]/[CH:21]=[CH:20]/[C@H:26]1[O:30][C:29]([CH3:32])([CH3:31])[O:28][C@H:27]1[CH2:33][O:34][CH2:35][C:36]([O:38][CH3:39])=[O:37]

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 71314246(2S,3E)-4-Bromo-1-(4-fluorophenoxy)but-3-en-2-olHCID 865887732-[[(4S,5R)-5-[(1E,3E)-1,3-hexadien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester

Product 1

HCID 865940532-[[(4S,5R)-5-[(1E,3E,7E,9S)-9-hydroxy-10-(4-fluorophenoxy)-1,3,7-decatrien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl esterYield 79.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

In a flame dried flask, a solution of (1E,3S)-1-bromo-4-(4-fluorophenoxy)-3-hydroxy-1-butene (0.84 g, 3 mmol), tetrakis(triphenylphosphine)palladium(0) (0.13 g, 0.2 mmol) and copper(I) iodide (60 mg, 0.3 mmol) in THF (50 mL) and diethylamine (5 mL, 48 mmol) was carefully deoxygenated by bubbling in argon gas for 45 minutes. The reaction was stirred as a solution of 2-[[(4S,5R)-5-[(1E,3E)-1,3-hexadien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester, (0.9 g, 3.2 mmol) in THF (50 mL), which had been deoxygenated by bubbling in argon for 45 minutes, was added. After about 4 hours, the reaction was complete. The reaction mixture was diluted with hexane and filtered through a pad of silica gel and the silica gel was eluted with ether. The combined filtrates were concentrated to give an oil. Purification by chromatography using a 20-75% gradient of ether in hexane gave 1.1 g of 2-[[(4S,5R)-5-[(1E,3E,7E,9S)-9-hydroxy-10-(4-fluorophenoxy)-1,3,7-decatrien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester, a compound of formula (EE), as an oil; 1H NMR (CDCl3) δ 1.37 (s, 3H), 1.5 (s, 3H), 3.52 (m, 2H), 3.75 (s, 3H), 3.83 (m, 2H), 4.13 (m, 2H), 4.44 (m, 1H), 5.74 (m, 1H), 5.76 (m, 2H), 6.05 (m, 1H), 6.17 (m, 1H), 6.29 (m, 1H), 6.58 (dd, 1H), 6.88 (m, 4H) ppm.

Workup

  1. customIn a flame dried flask
  2. customby bubbling in argon gas for 45 minutes
  3. customhad been deoxygenated
  4. customby bubbling in argon for 45 minutes
  5. additionwas added
  6. additionThe reaction mixture was diluted with hexane
  7. filtrationfiltered through a pad of silica gel
  8. washthe silica gel was eluted with ether
  9. concentrationThe combined filtrates were concentrated
  10. customto give an oil
  11. customPurification by chromatography

Sources & evidence

ORD record
ord-f1c94df03e264ec3b0ce87e26d03aeb8
Source dataset
uspto-grants-2011_04
Patent number
US07928255B2

Reaction notes

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