Hydrochloric Acid → (R)-2-(3-Chloro-phenoxy)-N-(2-hydroxy-1-phenyl-ethyl)-nicotinamide

HRID 844038Notes

Reaction equation

HRID 844038 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O.[OH:18][CH2:19][C@@H:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>S(Cl)(Cl)=O.N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH:27][C@H:20]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:19][OH:18])=[O:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 1347972-Amino-2-phenylethan-1-olHCID 122026412-(3-Chlorophenoxy)nicotinic acid

Product 1

HCID 53928194(R)-2-(3-Chloro-phenoxy)-N-(2-hydroxy-1-phenyl-ethyl)-nicotinamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 2-(3-chloro-phenoxy)-nicotinic acid (0.25 grams, 1.0 mmole) in thionyl chloride (10 ml) was heated to reflux. After 1 hour the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (5 ml) and added dropwise to a solution of (S)-2-hydroxy-1-phenyl ethylamine (0.14 grams, 1.0 mmole) in pyridine (5 ml) at 0° C. After 30 minutes the mixture was warmed to room temperature. After 1 hour the mixture was poured into 1 N hydrochloric acid and extracted with ethyl acetate. The combined organics were washed with 1 N hydrochloric acid followed by brine and dried over Na2SO4. Concentration under reduced pressure resulted in a yellow oil that was purified by chromatography on silica gel eluting with 1:1 ethyl acetate/hexane to give a colorless oil. Anal. calcd. for C20H17N2O3Cl: C, 65.13; H, 4.65; N, 7.60. Found: C, 65.20; H, 4.78; N, 7.38; M.S. m/z [M+] 369; 1H NMR (400 MHz, CDCl3) d 2.54 (s, broad, 1H), 3.95 (m, 2H), 5.32 (m, 1H), 7.23 (m, 10H), 8.22 (m, 1H), 8.58 (m, 2H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in tetrahydrofuran (5 ml)
  3. temperatureAfter 30 minutes the mixture was warmed to room temperature
  4. extractionextracted with ethyl acetate
  5. washThe combined organics were washed with 1 N hydrochloric acid
  6. dry with materialdried over Na2SO4
  7. concentrationConcentration under reduced pressure
  8. customresulted in a yellow oil that
  9. customwas purified by chromatography on silica gel eluting with 1:1 ethyl acetate/hexane
  10. customto give a colorless oil

Sources & evidence

ORD record
ord-44ecc6f9962a40a79d403409301d0811
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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