Triethylamine → 6-[4-(3-Oxo-propyl)-phenoxy]-nicotinamide

HRID 492327Notes

Reaction equation

HRID 492327 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:20]=[CH:19][C:8]([O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][N:11]=2)=[CH:7][CH:6]=1.C(N(CC)CC)C.S(=O)(=O)=O.N1C=CC=CC=1>CS(C)=O>[O:1]=[CH:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][N:11]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 168533Sulfur trioxide-pyridineHCID 597304116-[4-(3-Hydroxy-propyl)-phenoxy]-nicotinamide

Product 1

HCID 597301476-[4-(3-Oxo-propyl)-phenoxy]-nicotinamideYield 36%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Add 6-[4-(3-hydroxy-propyl)-phenoxy]-nicotinamide (0.4051 g, 1.488 mmol) to a stirred solution of triethylamine (0.620 mL, 4.45 mmol) and anhydrous dimethylsulfoxide (4.5 mL). Dissolve pyridine sulfur trioxide (0.7023 g, 4.413 mmol) in anhydrous dimethylsulfoxide (4.5 mL) and add this solution via a cannula to the above stirred solution under nitrogen. Stir the reaction at room temperature for 1 h under nitrogen. Pour the reaction into ice water (50 mL), extract with ethyl acetate (3× 50 mL), dry the ethyl acetate extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 100% ethyl acetate to yield 0.1428 g (36%) of 6-[4-(3-oxo-propyl)-phenoxy]-nicotinamide: mass spectrum (ion spray): m/z=271.2 (M+1); 1H NMR (CDCl3): 9.84 (t, 1H), 8.58 (d, 1H), 8.16 (dd, 1H), 7.26-7.23 (m, 2H), 7.09-7.05 (m, 2H), 6.95 (d, 1H), 6.02 (br s, 2H), 2.98 (t, 2H), 2.82 (t, 2H).

Workup

  1. customthe reaction at room temperature for 1 h under nitrogen
  2. additionPour
  3. extractionextract with ethyl acetate (3× 50 mL)
  4. dry with materialdry the ethyl acetate
  5. filtrationfilter
  6. concentrationconcentrate on a rotary evaporator
  7. customto give the crude product
  8. customThe crude product is purified by flash chromatography on silica gel eluting with 100% ethyl acetate

Sources & evidence

ORD record
ord-6c04dcacefa14973b50e5eaeff542113
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

Loading…