Dichloromethane → (3S,3aR,7R,7aS)-7-Allyl-6,7a-dimethoxy-3-methyl-3-(4-methylpent-3-en-1-yl)-2,3,3a,4,7,7a-hexahydro-2,7-methanobenzofuran

HRID 633647Notes

Reaction equation

HRID 633647 reaction equation
C(Cl)Cl.[CH2:4]([C:7]1([CH2:17][C@@H:18]2[O:20][C@@:19]2([CH3:27])[CH2:21][CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[C:12]([O:13][CH3:14])=[CH:11][CH2:10][CH:9]=[C:8]1[O:15][CH3:16])[CH:5]=[CH2:6].C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>CCOC(C)=O.CCCCCC>[CH2:4]([C@:7]12[CH2:17][CH:18]3[O:20][C@@:8]1([O:15][CH3:16])[C@@H:9]([C@:19]3([CH3:27])[CH2:21][CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[CH2:10][CH:11]=[C:12]2[O:13][CH3:14])[CH:5]=[CH2:6]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 65367Trimethylsilyl triflateHCID 988982,6-Di-tert-butyl-4-methylpyridineHCID 90124004(2S,3S)-3-((1-Allyl-2,6-dimethoxycyclohexa-2,5-dien-1-yl)methyl)-2-methyl-2-(4-methylpent-3-en-1-yl)oxirane

Product 1

HCID 90123929(3S,3aR,7R,7aS)-7-Allyl-6,7a-dimethoxy-3-methyl-3-(4-methylpent-3-en-1-yl)-2,3,3a,4,7,7a-hexahydro-2,7-methanobenzofuranYield 86.7%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A DCM (6 mL) solution of 8 (100 mg, 0.30 mmol, 1 equiv.) and 2,6-di-tert-butyl-4-methylpyridine (124 mg, 0.60 mmol, 2 equiv.) was cooled to −78° C. in a 20-mL scintillation vial, and trimethylsilyl trifluoromethanesulfonate (65 μL, 0.36 mmol, 1.2 equiv.) was added dropwise. Immediately upon this addition, the solution turned bright yellow. After stirring at −78° C. for 30 min, the reaction was quenched with saturated aqueous NaHCO3 and allowed to warm to room temperature. The mixture was then extracted four times with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to a slight yellow oil. Flash column chromatography (50 mL SiO2, 99:1 hexane:EtOAc) afforded 85 mg (0.26 mmol, 85% yield) of 9 as a clear, colorless oil. TLC Rf 0.53 (9:1 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 6.02 (ddt, J=17.2, 10.1, 7.1 Hz, 1H), 5.04 (t, J=7.1 Hz, 1H), 5.01-4.95 (m, 2H), 4.54 (dd, J=5.7, 2.1 Hz, 1H), 3.75 (d, J=5.3 Hz, 1H), 3.48 (s, 3H), 3.47 (s, 3H), 2.42 (dd, J=14.1, 7.3 Hz, 1H), 2.29 (dd, J=14.1, 7.0 Hz, 1H), 2.19 (ddd, J=18.1, 6.7, 2.2 Hz, 1H), 2.07-2.02 (m, 2H), 2.01-1.93 (m, 1H), 1.86 (dd, J=12.4, 5.3 Hz, 1H), 1.81 (d, J=12.4 Hz, 1H), 1.72-1.65 (m, 4H), 1.58 (s, 2H), 1.47-1.42 (m, 1H), 1.25-1.20 (m, 1H), 1.14 (s, 3H). 13C NMR (125 MHz; CDCl3): δ 158.1, 138.3, 131.7, 124.9, 115.8, 112.5, 90.7, 79.1, 54.6, 51.3, 46.3, 44.4, 42.0, 38.87, 38.72, 33.6, 28.1, 25.9, 22.9, 20.1, 17.8. IR (NaCl, thin film, cm−1) 2966, 2930, 1671, 1578, 1460, 1439, 1376, 1304, 1215, 1168, 1136, 1062, 1001, 906. HRMS-ESI (m/z): [M+Na]+ calculated for C21H32O3, 355.2244. found, 355.2245.

Workup

  1. additionImmediately upon this addition
  2. customthe reaction was quenched with saturated aqueous NaHCO3
  3. temperatureto warm to room temperature
  4. extractionThe mixture was then extracted four times with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a slight yellow oil

Sources & evidence

ORD record
ord-5e5495ee986b4c8bb2fd860cbe6a19f2
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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