Lithium Chloride → Ethyl (+/-)-10,11-dihydro-3-[4-(2-tetrahydropyranyloxy)-1-butyn-1-yl]-5H-dibenzo[a,d]cycloheptene-10-acetate

HRID 1369233Notes

Reaction equation

HRID 1369233 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[CH2:16][CH:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1)(=O)=O.[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:36][CH2:37][CH2:38][C:39]#[C:40][Sn](CCCC)(CCCC)CCCC.[Li+].[Cl-]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:36][CH2:37][CH2:38][C:39]#[C:40][C:7]1[CH:8]=[CH:9][C:10]2[CH2:16][CH:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 111022914-(2-Tetrahydropyranyloxy)-1-tributylstannyl-1-butyneHCID 15516627ethyl (+/-)-10,11-dihydro-3-(trifluoromethanesulfonyioxy)-5H-dibenzo[a,d]cycloheptene-10-acetate

Product 1

HCID 12071462Ethyl (+/-)-10,11-dihydro-3-[4-(2-tetrahydropyranyloxy)-1-butyn-1-yl]-5H-dibenzo[a,d]cycloheptene-10-acetateYield 83%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of ethyl (±)-10,11-dihydro-3-(trifluoromethanesulfonyloxy)-5H-dibenzo[a,d]cycloheptene-10-acetate (1.34 g, 3.13 mmole), 4-(2-tetrahydropyranyloxy)-1-tributylstannyl-1-butyne (1.66 g, 3.76 mmole), LiCl (398 mg, 9.39 mmole), bis(triphenylphosphine)palladium dichloride (110 mg, 0.094 mmole), and anhydrous dioxane (31 mL) was heated at reflux under argon. After 1.5 hr, the reaction was concentrated to remove most of the dioxane, and the residue was taken up in Et2O (100 mL). 10% KF (50 mL) was added and the mixture was stirred briskly for 0.5 hr. The aqueous layer was removed and the Et2O layer was filtered through a mixture of celite® and MgSO4. The filtrate was concentrated and the residue was chromatographed on silica gel (10% EtOAc/hexanes) to afford the title compound (1.12 g, 83%) as a pale yellow oil: TLC (20% EtOAc/hexanes) Rf0.40; 1H NMR (400 MHz, CDCl3) δ7.21-7.30 (m, 1 H), 7.06-7.20 (m, 5 H), 7.00 (d, J=7.8 Hz, 1 H), 4.69 (t, J=3.6 Hz, 1 H), 4.31 (d, J=15.2 Hz, 1 H), 4.11-4.23 (m, 2 H), 3.76-3.97 (m, 4 H), 3.59-3.68 (m, 1 H), 3.48-3.57 (m, 1 H), 3.34 (dd, J=15.2, 4.1 Hz, 1 H), 2.97 (dd, J=15.2, 9.5 Hz, 1 H), 2.70 (t, J=7.3 Hz, 2 H), 2.65 (dd, J=15.7, 4.8 Hz, 1 H), 2.51 (dd, J=15.7, 9.5 Hz, 1 H), 1.78-1.92 (m, 1 H), 1.68-1.78 (m, 1 H), 1.44-1.68 (m, 4 H), 1.27 (t, J=7.1 Hz, 3 H); MS (ES) m/e 455 (M+Na)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under argon
  3. concentrationthe reaction was concentrated
  4. customto remove most of the dioxane
  5. addition10% KF (50 mL) was added
  6. customThe aqueous layer was removed
  7. filtrationthe Et2O layer was filtered through a mixture of celite® and MgSO4
  8. concentrationThe filtrate was concentrated
  9. customthe residue was chromatographed on silica gel (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-dd01a2518cad470886e52d9419dfa39e
Source dataset
uspto-grants-2003_06
Patent number
US06576643B2

Reaction notes

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