Benzyl Bromide → HCID 178450844, compound

HRID 2253182Notes

Reaction equation

HRID 2253182 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([OH:19])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[C:20]1([CH2:26]Br)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CO[Na]>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([OH:19])[C:11]2[C:16]([C:17]=1[O:18][CH2:26][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 3

HCID 7498Benzyl BromideHCID 178418582HCID 178418582, compoundHCID 1784508431,4-Dihydroxy-isoquinoline-3-carboxylic acid butyl ester

Product 1

HCID 178450844HCID 178450844, compoundYield 30.7%

Procedure

A mixture of 1,4-dihydroxy-isoquinoline-3-carboxylic acid butyl ester (26.13 g, 100 mmol; Example D-20 b), PhCH2Br (18.2 ml, 150 mmol), MeONa (0.5 M in MeOH, 200 ml, 100 mmol) was stirred at ambient temperature for 48 h. Then the solvent was evaporated and EtOAc (100 ml) was added to the residue. The mixture was stirred vigorously for 10 min before it was filtered. The filtrate was washed with aqueous 2.5N NaOH (2×100 ml) and aqueous 2N HCl (1×100 ml). The organic phase was dried over MgSO4 and evaporated in vacuo. The residue was recrystallized from MeOH (500 ml)/water (300 ml). The resulting yellow solid was further purified by flash column chromatography on silica gel using hexanes:EtOAc:NEt3=65:30:5 as the eluent to give 10.8 g of a yellow solid. 2 g of this material were further purified by flash column chromatography on silica gel using hexanes:EtOAc:NEt3=75:20:5 as the eluent to give 1.57 g of the title compound as a slightly yellowish solid; 1H NMR (CDCl3): δ=8.88 (bs, 1H), 8.46 (d, 1H), 8.42 (d, 1H), 7.26 to 7.96 (m, 7H), 5.06 (s, 2H), 4.38 (t, 2H), 1.69 (m, 2H), 1.37 (m, 2H), 0.91 (t, 3H).

Workup

  1. customThen the solvent was evaporated
  2. additionEtOAc (100 ml) was added to the residue
  3. stirringThe mixture was stirred vigorously for 10 min before it
  4. filtrationwas filtered
  5. washThe filtrate was washed with aqueous 2.5N NaOH (2×100 ml) and aqueous 2N HCl (1×100 ml)
  6. dry with materialThe organic phase was dried over MgSO4
  7. customevaporated in vacuo
  8. customThe residue was recrystallized from MeOH (500 ml)/water (300 ml)
  9. customThe resulting yellow solid was further purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-b4b7f0f8432d4eafa2dfa2659e55201e
Source dataset
uspto-grants-2008_01
Patent number
US07323475B2

Reaction notes

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