Ethyl vinyl ether → 7-Bromo-6-[3-bromo-2-(1-ethoxyethoxy)-propoxy]-1-[(S)-2-(tert-butyldimethyl-silanyloxy)-propyl]-1H-indazole

HRID 2121883Notes

Reaction equation

HRID 2121883 reaction equation
[Br:1][CH2:2][CH:3]([OH:27])[CH2:4][O:5][C:6]1[C:14]([Br:15])=[C:13]2[C:9]([CH:10]=[N:11][N:12]2[CH2:16][C@@H:17]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH3:18])=[CH:8][CH:7]=1.[CH:28]([O:30][CH2:31][CH3:32])=[CH2:29]>ClCCl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:15][C:14]1[C:6]([O:5][CH2:4][CH:3]([O:27][CH:28]([O:30][CH2:31][CH3:32])[CH3:29])[CH2:2][Br:1])=[CH:7][CH:8]=[C:9]2[C:13]=1[N:12]([CH2:16][C@@H:17]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:21])[CH3:22])[CH3:18])[N:11]=[CH:10]2

Participants

5

Reactant 2

HCID 8023Ethyl vinyl etherHCID 695642801-Bromo-3-[7-bromo-1-[(S)-2-(tert-butyl-dimethyl-silanyloxy)-propyl]-1H-indazol-6-yloxy]-propan-2-ol

Product 1

HCID 695652487-Bromo-6-[3-bromo-2-(1-ethoxyethoxy)-propoxy]-1-[(S)-2-(tert-butyldimethyl-silanyloxy)-propyl]-1H-indazoleYield 85.1%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Step E (1.85 g, 3.54 mmol) and p-toluenesulfonic acid (0.01 g) in dichloromethane (50 mL) at 0° C. was added ethyl vinyl ether (1 mL, 10.5 mmol). After 30 min the reaction was quenched with a saturated solution of sodium bicarbonate (50 mL) and extracted with EtOAc (3×80 mL). Evaporation and purification by chromatography (silica, 1% to 8% EtOAc/hexane) gave a viscous oil (1.79 g, 81%): LC/MS (+APCI) m/z 595 (M+H).

Workup

  1. customAfter 30 min the reaction was quenched with a saturated solution of sodium bicarbonate (50 mL)
  2. extractionextracted with EtOAc (3×80 mL)
  3. customEvaporation and purification by chromatography (silica, 1% to 8% EtOAc/hexane)

Sources & evidence

ORD record
ord-4de30751c4e44d768666ac10dfa82a68
Source dataset
uspto-grants-2004_02
Patent number
US06696476B2

Reaction notes

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