Propyl mercaptan → HCID 11833689, compound

HRID 1956389Notes

Reaction equation

HRID 1956389 reaction equation
[H-].[Na+].C(S)CC.C1([O:12][C:13]2[CH:14]=[C:15]([C@@H:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:22][C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[CH:16]=[CH:17][C:18]=2[O:19][CH3:20])CCCC1>CN(C=O)C>[OH:12][C:13]1[CH:14]=[C:15]([C@@H:21]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:22][C:23]2[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 7848Propyl mercaptanHCID 24758Sodium hydrideHCID 1279284-{2-[3-(Cyclopentyloxy)-4-methoxyphenyl]-2-phenylethyl}pyridine

Product 1

HCID 11833689HCID 11833689, compoundYield 406.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of NaH (60% dispersion in mineral oil) (0.483 g, 12.075 mmol) in DMF under nitrogen at RT was added propanethiol (1.09 ml, 12.07 mmol) and the mixture stirred for 30 min. A solution of (R)-(+)-4-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl]pyridine (made as described in WO 94/14742) (1.8 g, 4.83 mmol) in DMF was added, the mixture heated to reflux for 5 h, allowed to cool (the reaction was followed by tic) and concentrated in vacuo. The residue was taken up in CH2Cl2 and washed with aqueous NaHCO3 solution. The aqueous phase was extracted with CH2Cl2, the combined organic phase dried (MgSO4), filtered and concentrated in vacuo. The residue was subjected to chromatography (SiO2 ; Et2O) then recrystallised (i-propylether) to give the title compound (6.00 g) as a white solid. m.p. 158°-159° C. (Found C, 79.37; H, 6.96; N, 3.66. C24H25O2N requires C, 80.19; H, 7.01; N, 3.90%). δH (CDCl3) 1.5-1.9 (8H, m, (CH2)4), 3.39 (2H, dd, J 8, 1 Hz, CH2 pyridine), 4.12 (1H, t, J 8 Hz, CHCH2), 4.62 (1H, m, OCH), 5.52 (1H, br s, OH), 6.57 (1H, m, C6H3), 6.6-6.7 (1H, m, C6H3), 6.75-6.8 (1H, m, C6H3), 6.91 (2H, d, J 6. Hz, H3, H5 pyridine), 7.1-7.3 (5H, m, C6H5), and 8.38 (2H, d, J 6 Hz, H2, H6 pyridine).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 5 h
  3. temperatureto cool (the reaction
  4. concentrationconcentrated in vacuo
  5. washwashed with aqueous NaHCO3 solution
  6. extractionThe aqueous phase was extracted with CH2Cl2
  7. dry with materialthe combined organic phase dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customthen recrystallised (i-propylether)

Sources & evidence

ORD record
ord-62af3768d831457c9f109c41e57899ea
Source dataset
uspto-grants-1998_07
Patent number
US05780478

Reaction notes

Loading…