HCID 21877402, compound → HCID 21877301, compound

HRID 1862110Notes

Reaction equation

HRID 1862110 reaction equation
Br[C:2]1([CH:9]=[CH:8][CH:7]=[CH:6][CH2:5]1)[CH:3]=[CH2:4].[Li]C(C)(C)C.[I:15][C:16]1[C:24]2[C:19](=[CH:20][C:21](I)=[CH:22][CH:23]=2)[N:18]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:17]=1>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[I:15][C:16]1[C:24]2[C:19](=[CH:20][C:21]([C:3]([C:2]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)=[CH2:4])=[CH:22][CH:23]=2)[N:18]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:17]=1

Participants

7

Reactant 3

HCID 21877402HCID 21877402, compoundHCID 21877513HCID 21877513, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 21877301HCID 21877301, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

1-Bromostyrene (26 μL, 0.20 mmol, 2.0 equiv) was dissolved in THF (0.75 nmL), cooled to −78° C. and was treated with t-BuLi (235 μL, 0.40 mmol, 1.70 M, 4.0 equiv). The mixture was allowed to warm to −42° C. for 10 min and was added to freshly dried zinc chloride (34 mg, 0.25 mmol, 2.5 equiv). The resulting solution was allowed to warm to 23° C. with stirring for 25 min. This mix was added to a mixture of neat 3,6-Diiodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole (50 mg, 0.10 mmol, 1 equiv) and Pd(PPh3)4 (5 mg, 0.004 mmol, 0.04 equiv). After 10 min the reaction was determined to be complete by TLC monitoring and was quenched with saturated sodium bicarbonate. Organic material was extracted into ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. Silica gel chromatography (5:95 ethyl acetate-hexane) provided 3-Iodo-6-(1-phenyl-vinyl)-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole (33.1 mg, 70%): Rfsm 0.39, p 0.36 (ethyl acetate-hexane 1:9); 1H NMR (300 MHz, CDCl3) δ 7.50 (s, 1H), 7.42 (d, 1H, J=8.4 Hz), 7.33 (m, 5H), 7.22 (dd, 1H, J=1.2, 8.4 Hz), 5.68 (s, 2H), 5.59 (d, 1H, J=1.0 Hz), 5.57 (d, 1H, J=1.0 Hz), 3.58 (t, 2H, J=8.2 Hz), 0.88 (t, 2H, J=8.2 Hz), −0.09 (s, 9H); HRMS (FAB) [m+H]/z Calc'd 477.0859, found 477.0866.

Workup

  1. temperatureto warm to −42° C. for 10 min
  2. temperatureto warm to 23° C.
  3. waitAfter 10 min the reaction was determined
  4. customwas quenched with saturated sodium bicarbonate
  5. extractionOrganic material was extracted into ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b309a488f3ee4afdadb66bf50203ef85
Source dataset
uspto-grants-2003_03
Patent number
US06534524B1

Reaction notes

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