Acetic Acid → HCID 59729992, compound

HRID 228395Notes

Reaction equation

HRID 228395 reaction equation
[CH2:1]1[C:10]2[C:5](=[C:6]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[CH2:21]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=2)[CH2:1]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59730223HCID 59730223, compound

Product 1

HCID 59729992HCID 59729992, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Combine 6-(1,2,3,4-tetrahydro-isoquinolin-5-yloxy)-nicotinamide (100 mg, 0.3 7 mmol), benzaldehyde (39 μL, 0.38 mmol), sodium triacetoxyborohydride (101 mg, 0.48 mmol), acetic acid (22 μL, 0.39 mmol), and 1,2-dichloroethane (5 mL) then stir at room temperature for 18 hours. Dilute the reaction with saturated aqueous sodium bicarbonate solution and extract with dichloromethane (3×25 mL). Dry the combined dichloromethane extracts with sodium chloride/magnesium sulfate, filter, and concentrate on a rotary evaporator to yield 45 mg of the crude product. The crude product is purified by flash column chromatography on silica gel eluting with (0.5% conc. ammonium hydroxide/5% ethanol) to (1% conc. ammonium hydroxide/10% ethanol) in chloroform to yield 6-(2-benzyl-1,2,3,4-tetrahydro isoquinolin-5-yloxy)-nicotinamide (31 mg, 0.09 mmol): m/z=360.1 (M+1); 3H NMR (DMSO-d6, 300.00 MHz): 8.56 (s, 1H); 8.16-8.12 (m, 1H); 7.38-7.15 (m, 6H); 6.94-6.89 (m, 3H); 6.17 (s, 2H); 3.74-3.61 (m, 4H); 2.69-2.66 (m, 4H), HPLC=99% (30/70 to 90/10 ACN/(0.1% TFA in water), Zorbax SB-Phenyl 4.6 mm×15 cm×5 micron, λ=254 nm).

Workup

  1. additionDilute
  2. extractionextract with dichloromethane (3×25 mL)
  3. dry with materialDry the combined dichloromethane
  4. filtrationfilter
  5. concentrationconcentrate on a rotary evaporator
  6. customto yield 45 mg of the crude product
  7. customThe crude product is purified by flash column chromatography on silica gel eluting with (0.5% conc. ammonium hydroxide/5% ethanol) to (1% conc. ammonium hydroxide/10% ethanol) in chloroform

Sources & evidence

ORD record
ord-edd3bfabfe624004ba434a836a2d4c29
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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