Ammonium Chloride → HCID 68599379, compound

HRID 1407517Notes

Reaction equation

HRID 1407517 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:2]1=2.C([Mg]Cl)(C)C.[Br:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[C:22](=[O:34])[C:21]2=[O:35].[Cl-].[NH4+]>ClCCl>[Br:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[C:22](=[O:34])[C:21]2([OH:35])[C:9]1[C:8]([OH:11])=[CH:7][C:3]2[O:4][CH2:5][CH2:6][O:1][C:2]=2[CH:10]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 91152732,3-Dihydro-1,4-benzodioxin-6-olHCID 28492568HCID 28492568, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 68599379HCID 68599379, compoundYield 101.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,3-dihydrobenzo[b][1,4]dioxin-6-ol (2.55 g, 16.8 mmol) in anhydrous dichloromethane (100 mL) at 0° C. added isopropylmagnesium chloride (2 M solution in tetrahydrofuran, 10.0 mL, 19.9 mmol). The solution was stirred at 0° C. for 20 min and 5-bromo-1-(pyridin-2-ylmethyl)-1H-indole-2,3-dione (4.85 g, 15.3 mmol) was added. The reaction mixture was stirred at ambient temperature for 16 h, saturated aqueous ammonium chloride (25 mL) was added and the mixture was concentrated in vacuo. The residue was triturated with ethyl acetate (250 mL) and the solid collected by filtration to afford 5-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1-(pyridin-2-ylmethyl)-1,3-dihydro-2H-indol-2-one (7.26 g, 98%) as a beige solid: 1H NMR (300 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.71 (d, J=4.9 Hz, 1H), 8.06 (dd, J=7.80 Hz, 1H), 7.63-7.55 (m, 2H), 7.52 (d, J=8.0 Hz, 1H), 7.35 (dd, J=8.3, 2.0 Hz, 1H), 7.20 (s, 1H), 6.99 (d, J=2.0 Hz, 1H), 6.82 (d, J=8.3 Hz, 1H), 6.16 (s, 2H), 5.09 (ABq, 2H), 4.20-4.10 (m, 4H).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 16 h
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe residue was triturated with ethyl acetate (250 mL)
  4. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-675b5c57721a4945bc88fb43f33f3d51
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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