Dibromomethane → HCID 57857071, compound

HRID 561746Notes

Reaction equation

HRID 561746 reaction equation
[S:1]1[C:5]([C@H:6]([O:32][Si:33]([C:46]([CH3:49])([CH3:48])[CH3:47])([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)/[CH:7]=[CH:8]/[C@H:9]2[C:13](=O)[CH2:12][C@H:11]([O:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[C@@H:10]2[CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:4][C:3]2[CH:50]=[CH:51][CH:52]=[CH:53][C:2]1=2.[CH2:54](Br)Br>C(Cl)Cl.C1COCC1.C(OCC)(=O)C.[Ti](Cl)(Cl)(Cl)Cl.C(Br)Br.[Zn].[Zn].Cl[Ti](Cl)(Cl)Cl>[S:1]1[C:5]([C@H:6]([O:32][Si:33]([C:46]([CH3:48])([CH3:47])[CH3:49])([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)/[CH:7]=[CH:8]/[C@H:9]2[C:13](=[CH2:54])[CH2:12][C@H:11]([O:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[C@@H:10]2[CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:4][C:3]2[CH:50]=[CH:51][CH:52]=[CH:53][C:2]1=2

Participants

9

Reactant 2

HCID 3024DibromomethaneHCID 57857057HCID 57857057, compound

Product 1

HCID 57857071HCID 57857071, compound

Reagents, catalysts & solvents 6

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 11144435HCID 11144435, compoundCatalyst2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(Z)-Methyl 7-((1R,2R,5S)-2-((R,E)-3-(benzo[b]thiophen-2-yl)-3-(tert-butyldiphenylsilyloxy)prop-1-enyl)-3-oxo-5-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enoate (15a, limiting reagent) is dissolved in DCM (0.05 M) under a nitrogen atmosphere and cooled to 0° C. A solution consisting of zinc methylene dibromide titanium tetrachloride is prepared by combining zinc dust (2.3 g) in THF (40 mL) with methylene dibromide (0.81 mL) at −40° C. under a nitrogen atmosphere. To the suspension is slowly added TiCl4 (0.92 mL). Portions (2 mL) of the zinc methylene dibromide titanium tetrachloride solution are added until the reaction is complete as judged by TLC. Upon completion, the reaction mixture is diluted with ethyl acetate and filtered twice through a bed of Celite. The filtrate is washed with a saturated aqueous solution of sodium bicarbonate, then with a 50% aqueous solution of brine. The organic phase is dried over sodium sulfate, filtered, and the solvent is evaporated. The crude product is purified by flash chromatography on regular silica gel eluted with hexanes-ethyl acetate to afford the title intermediate 17a.

Workup

  1. customis prepared
  2. customat −40° C.
  3. filtrationfiltered twice through a bed of Celite
  4. washThe filtrate is washed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent is evaporated
  8. customThe crude product is purified by flash chromatography on regular silica gel
  9. washeluted with hexanes-ethyl acetate

Sources & evidence

ORD record
ord-6432e302b3a74a85af48a87d07e413af
Source dataset
uspto-grants-2011_11
Patent number
US08063240B2

Reaction notes

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