Triethylamine → (3aR,4R,5R,6aS)-4-((E)-4-(3-Chlorophenoxy)-3-oxobut-1-en-1-yl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

HRID 1377834Notes

Reaction equation

HRID 1377834 reaction equation
COP([CH2:7][C:8](=[O:18])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)(=O)OC.[Li+].[Cl-].CCN([CH2:26][CH3:27])CC.[NH4+].[Cl-].[C:30]([O:33][CH2:34][CH3:35])(=[O:32])[CH3:31]>C(Cl)Cl.C1COCC1>[C:30]([O:33][C@@H:34]1[CH2:35][C@@H:34]2[O:33][C:30](=[O:32])[CH2:31][C@@H:35]2[C@H:26]1/[CH:27]=[CH:7]/[C:8](=[O:18])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)(=[O:32])[C:31]1[CH:15]=[CH:16][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 3566446Dimethyl 3-(3-chlorophenoxy)-2-oxopropylphosphonateHCID 86583716Ammonium chloride ethyl acetate

Product 1

HCID 12041488(3aR,4R,5R,6aS)-4-((E)-4-(3-Chlorophenoxy)-3-oxobut-1-en-1-yl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoateYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Phosphonate 11 (20.5 g, 70.0 mmol), 2.6 g (62 mmol) of LiCl, and 200 mL of THF were mixed together at 0° C. and 6.10 g (60.4 mmol) of NEt3 was added. Aldehyde 12 (14.0 g, 51.1 mmol) dissolved in 50 mL of CH2Cl2 was then added dropwise. After 1 h, the reaction was poured into 200 mL of a 1/1 mixture of saturated NH4Cl/ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). Combined organic layers were dried over MgSO4, filtered, concentrated, and the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2, to afford 16.2 g (72%) of 13 as a white crystalline solid, m.p.=101.0°-102.0° C. 1H NMR δ 8.0-7.9 (m, 2H), 7.62-7.52 (m, 1H), 7.50-7.38 (m, 2H), 7.18 (t, J=8.2 Hz, 1H), 7.0-6.82 (m, 3H), 6.75-6.70 (m, 1H), 6.54 (d, J=15.1 Hz, 1H), 5.32 (q, J=6.2 Hz, 1H), 5.12-5.05 (m, 1H), 4.66 (s, 2H), 3.0-2.8 (m, 3H), 2.7-2.2 (m, 3H).

Workup

  1. additionwas then added dropwise
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  4. dry with materialCombined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2

Sources & evidence

ORD record
ord-5775b4f1bee74375847199b4c2d63006
Source dataset
uspto-grants-1997_09
Patent number
US05665773

Reaction notes

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