Benzyl Bromide → 2-(3-(benzyloxy)-6-chloropyridin-2-yl)-4-fluoro-1H-indole

HRID 1776824Notes

Reaction equation

HRID 1776824 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([OH:18])=[CH:4][CH:3]=1.[CH:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH2:25]([O:18][C:5]1[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:22]1[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 867282372-(3-(benzyloxy)-6-chloropyridin-2-yl)-4-fluoro-1H-indoleYield 74.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (100 mg, 0.38 mmol, prepared using similar method described in Example 1), BnBr (97 mg, 0.572 mmol) and K2CO3 (158 mg, 1.146 mmol) in DMF (1 mL) was stirred at room temperature overnight. The mixture was then concentrated in vacuo. The resulting resulting residue was diluted with water (15 mL) and extracted with ethyl acetate (10 mL×3). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using Prep-TLC (petroleum ether:EA=3:1) to provide 2-(3-(benzyloxy)-6-chloropyridin-2-yl)-4-fluoro-1H-indole (100 mg, yield: 74.6%). 1H-NMR (CDCl3, 400 MHz) δ 9.64 (s, 1H), 7.12˜7.48 (m, 10H), 6.76 (t, J=8.8 Hz, 1H), 5.33 (s, 2H). MS (M+H)+: 353/355.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customThe resulting resulting residue
  3. extractionextracted with ethyl acetate (10 mL×3)
  4. washThe organic layer was washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-66a525b72a0a40339e91a781612f94dc
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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