2-Bromonaphthalene → HCID 21877272, compound

HRID 1861056Notes

Reaction equation

HRID 1861056 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.[Li]CCCC.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:39]=[C:38]3[C:34]([C:35](I)=[N:36][N:37]3[S:40]([C:43]3[C:48]([CH3:49])=[CH:47][C:46]([CH3:50])=[CH:45][C:44]=3[CH3:51])(=[O:42])=[O:41])=[CH:33][CH:32]=2)=[CH:27][C:26]=1[O:53][CH3:54])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)(O)[O-].[Na+]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:39]=[C:38]3[C:34]([C:35]([C:2]4[CH:11]=[CH:10][C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH:3]=4)=[N:36][N:37]3[S:40]([C:43]3[C:48]([CH3:49])=[CH:47][C:46]([CH3:50])=[CH:45][C:44]=3[CH3:51])(=[O:42])=[O:41])=[CH:33][CH:32]=2)=[CH:27][C:26]=1[O:53][CH3:54])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 113722-BromonaphthaleneHCID 516892Sodium BicarbonateHCID 21877467HCID 21877467, compoundHCID 178418339Butyllithium

Product 1

HCID 21877272HCID 21877272, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2-Bromonaphthalene (117 mg, 0.564 mmol, 6.0 equiv) was dissolved in THF (0.75 mL) and cooled to −78° C. The mixture was treated with n-BuLi (226 μL, 2.5 M, 6.0 equiv) and was allowed to stir at −78° C. for 30 min. The mixture was then added to freshly dried ZnCl2 solid (139 mg, 0.80 mmol, 8.5 equiv) via cannula and the resulting mix was allowed to warm to 23° C. (during the addition the yellow color disappears). After 30 min at 23° C. the mixture is added to a mixture of 6-(4-benzyloxy-3-methoxy-phenyl)-3-iodo-1-(2,4,6-trimethyl-benzenesulfonyl)-1H-indazole (60 mg, 0.094 mmol, 1 equiv) and Pd(PPh3)4 (6 mg, 0.005 mmol, 0.05 equiv) via cannula. The resulting solution was allowed to stir for 16 h. Saturated sodium bicarbonate was added and the mixture was partitioned between saturated sodium bicarbonate (15 mL) and ethyl acetate (15 mL). The organic material was dried over sodium sulfate, decanted and concentrated. Purification by silica gel chromatography (1:9-2:8 ethyl acetate-hexane) gave 6-(4-benzyloxy-3-methoxy-phenyl)-3-naphthalen-2-yl-1-(2,4,6-trimethyl-benzenesulfonyl)-1H-indazole as a solid (42 mg, 70%): Rf sm 0.4, p 0.4 (ethyl acetate-hexane 3:7); 1H NMR (CDCl3) δ 8.44 (s, 1H), 8.41 (s, 1H), 8.12 (d, 1H, J=8 Hz), 8.05-7.00 (m, 17H), 5.30 (s, 2H), 4.02 (s, 3H), 2.80 (s, 3H), 2.34 (s, 3H).

Workup

  1. additionthe resulting mix
  2. temperatureto warm to 23° C. (
  3. additionduring the addition the yellow color
  4. stirringto stir for 16 h
  5. customthe mixture was partitioned between saturated sodium bicarbonate (15 mL) and ethyl acetate (15 mL)
  6. dry with materialThe organic material was dried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (1:9-2:8 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-d762e19673ef482c8568cddf0e3efdc1
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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