Ethanethiol → HCID 178517708, compound

HRID 1490205Notes

Reaction equation

HRID 1490205 reaction equation
[H-].[Na+].C(S)C.[CH:6]1[C:19]2[C:18]3([CH2:21][N:22]4[CH2:27][CH2:26][C:25]([C:29]5[C:30]([O:35]C)=[N:31][CH:32]=[CH:33][CH:34]=5)([OH:28])[CH2:24][CH2:23]4)[CH2:20][CH:11]([C:12]4[C:17]3=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:10]=2[CH:9]=[CH:8][CH:7]=1>CN(C)C=O.O>[OH:35][C:30]1[C:29]([C:25]2([OH:28])[CH2:24][CH2:23][N:22]([CH2:21][C:18]34[CH2:20][CH:11]([C:12]5[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=53)[C:10]3[C:19]4=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:27][CH2:26]2)=[CH:34][CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 3

HCID 6343EthanethiolHCID 24758Sodium hydrideHCID 214806551-(9,10-Dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(2-methoxy-3-pyridyl)piperidin-4-ol

Product 1

HCID 178517708HCID 178517708, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a dimethylformamide solution (3.5 mL) of sodium hydride (60% in mineral oil, 58 mg, 1.46 mmol, 2.5 eq) under nitrogen was added ethanethiol (0.108 mL, 1.46 mmol, 2.5 eq) via gas tight syringe. Once gas evolution had ceased, a solution of 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(2-methoxy-3-pyridyl)piperidin-4-ol (described in example 32) (240 mg, 0.58 mmol) in dimethylformamide (2.0 mL) was added in a single portion. After the reaction had refluxed for 2 h, it was cooled to room temperature and diluted with water (25 mL). The resulting precipitate was filtered and purified by flash chromatography over silica gel (140 mL, eluent: 15% methanol in methylene chloride) to yield 190 mg (83%) of the title compound as a white solid. TLC analysis (Rf 0.10, 15% methanol in methylene chloride). 1H NMR (CDCl3, 300 HHz) 7.36 (dd, J=2.0, 7.2 Hz, 1H), 7.23 (m, 5H), 6.94 (m,4H), 6.31 (dd, J=6.7, 6.8 Hz, 1H), 5.82 (s, 1H), 4.27 (s, 1H), 3.48 (s, 2H), 2.84 (m, 2H), 2.61 (d, J=1.4 Hz, 1H), 2.00 (m, 2H), 1.89 (m, 2H) MS (CI, CH4) m/z 399 (M+1,100), 427 (M+29,7), 381 (18) The free base was dissolved in methanol/methylene chloride, acidified with ethereal HCl and the hydrochloride salt was precipitated by ether dilution. The salt was filtered, rinsed with fresh diethyl ether, and dried in vacuo (50° C., 75 pascal, 18 h) to yield a white solid, mp 195°-199° C.

Workup

  1. temperatureAfter the reaction had refluxed for 2 h
  2. filtrationThe resulting precipitate was filtered
  3. custompurified by flash chromatography over silica gel (140 mL, eluent: 15% methanol in methylene chloride)

Sources & evidence

ORD record
ord-587bd37780874765b8005aee5dd8f03d
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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