1,5-Dimethoxy-6-(3-methylbut-2-en-1-yl)cyclohexa-1,4-diene → (2S,3S)-3-((2,6-Dimethoxy-1-(3-methylbut-2-en-1-yl)cyclohexa-2,5-dien-1-yl)methyl)-2-(4-methoxy-4-methylpentyl)-2-methyloxirane

HRID 633656Notes

Reaction equation

HRID 633656 reaction equation
[CH3:1][O:2][C:3]1[CH:8]([CH2:9][CH:10]=[C:11]([CH3:13])[CH3:12])[C:7]([O:14][CH3:15])=[CH:6][CH2:5][CH:4]=1.C([Li])(CC)C.Br[CH2:22][C@@H:23]1[O:25][C@:24]1([CH2:27][CH2:28][CH2:29][C:30]([O:33][CH3:34])([CH3:32])[CH3:31])[CH3:26]>CCOC(C)=O.CCCCCC.C1COCC1.C1CCCCC1>[CH3:15][O:14][C:7]1[C:8]([CH2:22][C@@H:23]2[O:25][C@:24]2([CH2:27][CH2:28][CH2:29][C:30]([O:33][CH3:34])([CH3:32])[CH3:31])[CH3:26])([CH2:9][CH:10]=[C:11]([CH3:13])[CH3:12])[C:3]([O:2][CH3:1])=[CH:4][CH2:5][CH:6]=1

Participants

8

Reactant 3

HCID 710781221,5-Dimethoxy-6-(3-methylbut-2-en-1-yl)cyclohexa-1,4-dieneHCID 86718447(2S,3R)-3-(Bromomethyl)-2-(4-methoxy-4-methylpentyl)-2-methyloxirane2×HCID 178418400CID 53628100

Product 1

HCID 86718446(2S,3S)-3-((2,6-Dimethoxy-1-(3-methylbut-2-en-1-yl)cyclohexa-2,5-dien-1-yl)methyl)-2-(4-methoxy-4-methylpentyl)-2-methyloxiraneYield 67%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

A THF (100 mL) solution of 11 (4.35 g, 20.9 mmol, 1 equiv.) was cooled to −78° C. in a 250-mL round-bottom flask, and a cyclohexane solution of sec-butyllithium (1.21 M, 21.6 mL, 26.1 mmol, 1.25 equiv.) was added slowly over 5 min. The resulting yellow slurry was warmed to −30° C. over 40 min and maintained at that temperature for an additional 15 min. The resulting dark orange-red slurry was cooled to −78° C., and a THF (20 mL) solution of 29 (4.98 g, 18.8 mmol, 0.9 equiv.) was added, followed by two THF (10 mL) rinses of the flask that contained 29. At the end of the initial addition of 29, the slurry became faint yellow, and it was allowed to warm slowly to 0° C. over 3.5 h. The slurry was then quenched with H2O at 0° C., producing a mild effervescence. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a yellow oil. Flash column chromatography (400 mL SiO2, 9:1 to 8:2 hexane:EtOAc) afforded 4.95 g (12.6 mmol, 67% yield) of 30 as a colorless oil. TLC Rf 0.38 (8:2 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 4.89 (t, J=7.3 Hz, 1H), 4.76 (t, J=3.5 Hz, 1H), 4.72 (t, J=3.5 Hz, 1H), 3.51 (s, 3H), 3.46 (s, 3H), 3.15 (s, 3H), 2.75 (t, J=3.6 Hz, 2H), 2.61 (dd, J=8.0, 3.9 Hz, 1H), 2.34-2.27 (m, 2H), 2.03 (dd, J=13.7, 3.9 Hz, 1H), 1.76 (dd, J=13.7, 8.0 Hz, 1H), 1.62 (s, 3H), 1.54 (s, 3H), 1.51 (m, J=11.0, 5.5, 2.8 Hz, 1H), 1.42-1.37 (m, 2H), 1.35-1.30 (m, 2H), 1.27-1.22 (m, 1H), 1.17 (s, 3H), 1.12 (s, 6H). 13C NMR (126 MHz; CDCl3): δ 154.07, 154.01, 132.5, 120.7, 93.04, 92.93, 74.6, 61.46, 61.26, 54.5, 54.1, 49.3, 46.2, 40.10, 39.90, 34.6, 34.1, 26.1, 25.22, 25.16, 24.2, 19.8, 17.8, 16.8. FTIR (thin film) νmax: 2972, 2912, 2828, 1695, 1659, 1453, 1381, 1364, 1223, 1206, 1151, 1124, 1084, 1033, 973, 952, 849, 779, 689 cm−1. HRMS-ESI (m/z): [M+H]+ calculated for C24H40O4, 393.2999. found, 393.3000.

Workup

  1. temperaturemaintained at that temperature for an additional 15 min
  2. temperatureThe resulting dark orange-red slurry was cooled to −78° C.
  3. temperatureto warm slowly to 0° C. over 3.5 h
  4. customThe slurry was then quenched with H2O at 0° C.
  5. customproducing a mild effervescence
  6. temperatureThe mixture was warmed to room temperature
  7. extractionextracted thrice with EtOAc
  8. washwashed with H2O and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo to a yellow oil

Sources & evidence

ORD record
ord-db990af6c453400198335cd8e1e831bc
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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