Dichloromethane → (1S,5R,7S,8S,9S)-7,9-Dihydroxy-4,9-dimethoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-en-2-one

HRID 633660Notes

Reaction equation

HRID 633660 reaction equation
C(Cl)Cl.[CH3:4][O:5][C:6]1[C@@:7]2([CH2:34][CH:35]=[C:36]([CH3:38])[CH3:37])[CH2:13][CH:11]3[O:12][C@@:8]2([O:32][CH3:33])[C@H:9]([C:29](=[O:31])[CH:30]=1)[C@:10]3([CH3:28])[CH2:14][CH2:15][CH2:16][C:17]([CH3:27])([O:19][Si:20]([CH2:25][CH3:26])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH3:18].C(N(CC)CC)C.BrB(C)C.CC[O:52]C(C)=O>CCCCCC>[OH:12][C@@H:11]1[C@@:10]([CH3:28])([CH2:14][CH2:15][CH2:16][C:17]([CH3:18])([O:19][Si:20]([CH2:21][CH3:22])([CH2:23][CH3:24])[CH2:25][CH3:26])[CH3:27])[C@@H:9]2[C@:8]([OH:52])([O:32][CH3:33])[C@@:7]([CH2:34][CH:35]=[C:36]([CH3:37])[CH3:38])([C:6]([O:5][CH3:4])=[CH:30][C:29]2=[O:31])[CH2:13]1

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 123224DimethylboronbromideHCID 86718449(3S,3aS,7R,7aS)-6,7a-Dimethoxy-3-methyl-3-(4-methyl-4-((triethylsilyl)oxy)pentyl)-7-(3-methylbut-2-en-1-yl)-3,3a,7,7a-tetrahydro-2,7-methanobenzofuran-4(2H)-one

Product 1

HCID 71520048(1S,5R,7S,8S,9S)-7,9-Dihydroxy-4,9-dimethoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-en-2-oneYield 57%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

A DCM (20 mL) solution of 38 (794 mg, 1.57 mmol, 1 equiv.) and triethylamine (131 μL, 0.940 mmol, 0.6 equiv.) was cooled to −95° C. in a 100-mL recovery flask, and a DCM solution of bromodimethylborane (1.59 M, 5.9 mL, 9.4 mmol, 6 equiv.) was added slowly over 5 min. The resulting bright yellow solution was stirred at −95° C.±3° C. for 10 min, whereupon it was quenched through the sequential addition of NEt3 (6 mL) and saturated aqueous NaHCO3 at −95° C. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed successively with 2 N HCl, H2O, saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a yellow foam. Flash column chromatography (150 mL SiO2, 8:2 to 7:3 hexane:EtOAc) afforded 471 mg (0.897 mmol, 57% yield) of 39 as a white flocculent solid. TLC Rf 0.30 (7:3 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 5.46 (s, 1H), 5.26 (d, J=10.3 Hz, 1H), 3.74 (s, 3H), 3.61 (dd, J=11.8, 5.3 Hz, 1H), 3.55 (s, 1H), 3.25 (s, 3H), 2.87-2.82 (m, 2H), 2.25 (d, J=14.2 Hz, 1H), 1.95 (t, J=12.4 Hz, 1H), 1.73 (s, 3H), 1.70-1.65 (m, 4H), 1.43 (td, J=13.0, 4.2 Hz, 1H), 1.39-1.35 (m, 1H), 1.32-1.27 (m, 3H), 1.21 (s, 3H), 1.20 (s, 3H), 1.09 (s, 3H), 0.93 (t, J=7.9 Hz, 9H), 0.55 (q, J=7.6 Hz, 6H). 13C NMR (126 MHz; CDCl3): δ 198.2, 176.0, 137.4, 122.1, 104.1, 100.6, 73.8, 73.3, 57.6, 56.5, 51.1, 48.5, 45.9, 40.9, 39.4, 37.0, 30.8, 30.0, 29.4, 26.2, 18.0, 17.0, 7.3, 7.0. HRMS-ESI (m/z): [M+Na]+ calculated for C29H52O6Si, 547.3425. found, 547.3404.

Workup

  1. customwas quenched through the sequential addition of NEt3 (6 mL) and saturated aqueous NaHCO3 at −95° C
  2. extractionextracted thrice with EtOAc
  3. washwashed successively with 2 N HCl, H2O, saturated aqueous NaHCO3, and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a yellow foam

Sources & evidence

ORD record
ord-3af29a81abe04ab09722925dfba016e2
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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