Ammonium Chloride → HCID 58123261, compound

HRID 1948677Notes

Reaction equation

HRID 1948677 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:20]=[C:19]2[C:15]([CH2:16][CH2:17][C:18]2=[O:21])=[CH:14][CH:13]=1.[Cl-].[NH4+]>O1CCCC1>[Br:11][C:12]1[CH:20]=[C:19]2[C:15]([CH2:16][CH2:17][C:18]2([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[OH:21])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 1397781-Indanone, 6-bromo-HCID 178491912HCID 178491912, compound

Product 1

HCID 58123261HCID 58123261, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

6.4 ml (6.4 mmol) of a solution of 4-methoxyphenylmagnesium bromide in tetrahydrofuran (1M soln) are added dropwise to a solution of 0.9 g (4.26 mmol) of 6-bromo-1-indanone in 10 ml of absolute tetrahydrofuran under nitrogen at −20° C. The reaction solution is subsequently warmed to room temperature over the course of 12 hours, then 45 ml of 10% ammonium chloride solution are added, and finally the mixture is extracted twice with 20 ml of methylene chloride each time. After the combined organic phases have been dried over sodium sulfate and the solvent has been stripped off, the crude product is purified by column chromatography on silica gel (petroleum ether/ethyl acetate 4:1), giving 1.1 g of 6-bromo-1-(4-methoxyphenyl)indan-1-ol as pale-yellow oil. LC/MS: 302 (M+H-18 (water)). This oil is then dissolved in 20 ml of methylene chloride, the solution is cooled to −20° C., and, after addition of 0.8 ml (5 mmol) of triethylsilane, 0.53 ml (4.2 mmol) of boron trifluoride/diethyl ether complex is added. The reaction solution is subsequently warmed to room temperature, stirred at room temperature for four hours and then washed successively with 20 ml of saturated sodium hydrogencarbonate solution and 20 ml of saturated sodium chloride solution. After the methylene chloride solution has been dried over sodium sulfate and the solvent has been stripped off, the crude product is purified by column chromatography on silica gel (petroleum ether/ethyl acetate 95:5), giving 0.52 g of 6-bromo-1-(4-methoxyphenyl)indane as colourless oil; 1H-NMR (d6-DMSO): δ 7.34 ppm (d, 1H, J=7.9 Hz), 7.26 ppm (d, 1H, J=7.9 Hz), 7.11 ppm (d, 2H, J=8.97 Hz), 6.93 ppm (s, 1H), 6.90 ppm (d, 2H, J=8.97 Hz), 4.31 ppm (t, 1H, J=8.27 Hz), 3.74 ppm (s, 3H, OCH3), 2.98 ppm (m, 1H), 2.85 ppm (m, 1H), 2.48 ppm (m, 1H), 2.0 ppm (m, 1H).

Workup

  1. extractionfinally the mixture is extracted twice with 20 ml of methylene chloride each time
  2. dry with materialAfter the combined organic phases have been dried over sodium sulfate
  3. customthe crude product is purified by column chromatography on silica gel (petroleum ether/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-147c8e512d054db081886a00b92931f2
Source dataset
uspto-grants-2013_03
Patent number
US08399509B2

Reaction notes

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