1,2-Dichloroethane → 1-chloro-3-bromo-4-methoxy Isoquinoline

HRID 339158Notes

Reaction equation

HRID 339158 reaction equation
[Br:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11]1[C:20]2C(=[CH:16][CH:17]=[CH:18][CH:19]=2)C=[N:13][CH:12]=1.[Cl:21][CH2:22][CH2:23]Cl>>[Cl:21][C:22]1[C:23]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([O:10][CH3:9])=[C:12]([Br:1])[N:13]=1

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 67184N-bromobutanimide4×HCID 37854894-Methoxyisoquinoline

Product 1

HCID 222501171-chloro-3-bromo-4-methoxy Isoquinoline

Procedure

The material (Example 222a) was subjected to NBS bromination, thus 4-methoxy isoquinoline (Example 222a, 2.1 gm, 13.2 mmol) in 1,2-dichloroethane (DCE, 150 mL) was treated with N-bromosuccinimide (NBS, 1.5 gm, 8.4 mmol, 0.6×) at 70° C. for an hr followed by addition of second portion of 1.5 gm NBS. The dark brownish mixture was stirred for another hr before the addition of third portion of 1.0 gm NBS. The bromination was monitored by LC-MS until there was no starting material left. The crude mixture was evaporated to dryness and the desired product was filtered over a short bed of silica-gel (Type-H, Merck, 3 cm diameter by 1.5 cm height) eluted with straight hexanes first followed by gradually increasing the amount of ether. The desired product, (Example 222b), was isolated as an oily material (1.7 gm, 54%). LC/MS Rt-min (MH+) [method C]: 2.65 (238). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 4.04 (s, 3H) 7.64 (t, J=7.58 Hz, 1H) 7.76 (t, J=7.09 Hz, 1H) 7.99 (d, J=8.31 Hz, 1H) 8.11 (d, J=8.31 Hz, 1H) 8.85 (s, 1H). [3-Bromo-4-methoxy isoquinoline was previously prepared by a different procedure: Finkentey, Christel; Langhals, Elke; Langhals, Heinz. Chemische Berichte (1983), 116(6), 2394-7. NMR of the product was identical to that reported].

Workup

  1. waitleft
  2. customThe crude mixture was evaporated to dryness
  3. filtrationthe desired product was filtered over a short bed of silica-gel (Type-H, Merck, 3 cm diameter by 1.5 cm height)
  4. washeluted with straight hexanes
  5. temperatureby gradually increasing the amount of ether

Sources & evidence

ORD record
ord-608ac4a761914297aa047b0ea77a707b
Source dataset
uspto-grants-2014_11
Patent number
US08889871B2

Reaction notes

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