Dimethylboronbromide → (1S,5R,7S,8S)-8-(4-Bromo-4-methylpentyl)-7-hydroxy-4,9,9-trimethoxy-8-methyl-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-en-2-one

HRID 633659Notes

Reaction equation

HRID 633659 reaction equation
[CH3:1][O:2][C:3]1[C@@:4]2([CH2:25][CH:26]=[C:27]([CH3:29])[CH3:28])[CH2:10][CH:8]3[O:9][C@@:5]2([O:23][CH3:24])[C@H:6]([C:20](=[O:22])[CH:21]=1)[C@@:7]3([CH2:12][CH2:13][CH2:14][C:15](OC)([CH3:17])[CH3:16])[CH3:11].[Br:30]B(C)C.[C:34]([O-:37])(O)=O.[Na+]>CCOC(C)=O.CCCCCC.CO.CCN(CC)CC.C(Cl)Cl>[Br:30][C:15]([CH3:17])([CH3:16])[CH2:14][CH2:13][CH2:12][C@@:7]1([CH3:11])[C@@H:6]2[C:5]([O:37][CH3:34])([O:23][CH3:24])[C@@:4]([CH2:25][CH:26]=[C:27]([CH3:28])[CH3:29])([C:3]([O:2][CH3:1])=[CH:21][C:20]2=[O:22])[CH2:10][C@@H:8]1[OH:9]

Participants

9

Reactant 3

HCID 123224DimethylboronbromideHCID 516892Sodium BicarbonateHCID 90123914(3S,3aS,7R,7aS)-6,7a-Dimethoxy-3-(4-methoxy-4-methylpentyl)-3-methyl-7-(3-methylbut-2-en-1-yl)-3,3a,7,7a-tetrahydro-2,7-methanobenzofuran-4(2H)-one

Product 1

HCID 90123681(1S,5R,7S,8S)-8-(4-Bromo-4-methylpentyl)-7-hydroxy-4,9,9-trimethoxy-8-methyl-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-en-2-oneYield 47%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A DCM (3 mL) solution of 32 (160. mg, 0.316 mmol, 1 equiv.) and triethylamine (26.5 μL, 0.189 mmol, 0.6 equiv.) was cooled to −78° C. in a 10-mL recovery flask, and a DCM solution of bromodimethylborane (1.26 M, 1.5 mL, 1.89 mmol, 6 equiv.) was added slowly. After stirring the bright yellow solution at −78° C. for 40 min, a 1:1 mixture of NEt3 and MeOH (3 mL) and saturated aqueous NaHCO3 were added in succession at −78° C. The mixture was then allowed to warm to room temperature and thrice extracted with EtOAc. The organic extracts were combined, washed successively with saturated aqueous NH4Cl, H2O, and brine, dried over Na2SO4, filtered, and concentrated in vacuo to an off-white foam. Flash column chromatography (60 mL SiO2, 7:3 hexane:EtOAc) afforded 73 mg (0.15 mmol, 47% yield) of 33 as a white flocculent solid. TLC Rf 0.17 (7:3 hexane:EtOAc). 1H NMR (600 MHz; C6D6): δ 5.59 (t, J=7.0 Hz, 1H), 5.39 (s, 1H), 3.59 (dd, J=11.8, 5.2 Hz, 1H), 3.07 (s, 1H), 3.03 (s, 3H), 3.02 (s, 3H), 2.98 (s, 3H), 2.76 (dd, J=15.4, 7.6 Hz, 1H), 2.44 (dd, J=15.4, 6.2 Hz, 1H), 2.29-2.22 (m, 1H), 1.91 (t, J=12.4 Hz, 1H), 1.82 (dtd, J=15.4, 10.2, 5.1 Hz, 2H), 1.74-1.71 (m, 13H), 1.60 (s, 3H), 1.21 (s, 3H). 13C NMR (126 MHz; C6D6): δ 197.0, 178.3, 130.8, 123.2, 104.2, 103.5, 73.2, 68.5, 58.9, 55.7, 52.5, 50.8, 50.2, 48.7, 40.7, 40.0, 36.4, 35.3, 30.9, 26.1, 20.3, 18.6, 17.7. HRMS-ESI (m/z): [M+H]+ calculated for C24H39BrO5, 487.2054. found, 487.2050.

Workup

  1. additionwere added in succession at −78° C
  2. temperatureto warm to room temperature
  3. extractionthrice extracted with EtOAc
  4. washwashed successively with saturated aqueous NH4Cl, H2O, and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to an off-white foam

Sources & evidence

ORD record
ord-e7d862cc963e42b9afb38e9853d8875d
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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