Sodium hydride → HCID 12694071, compound

HRID 647542Notes

Reaction equation

HRID 647542 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[CH2:7][S:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2F)[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1.[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]\[C:29]([OH:31])=[O:30]>CS(C)=O.CCOCC>[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]\[C:29]([OH:31])=[O:30].[F:3][C:4]1[CH:5]=[C:6]([CH:7]2[S:8][C:9]3([CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]2=3)[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 444266Maleic AcidHCID 12694041HCID 12694041, compound

Product 1

HCID 12694071HCID 12694071, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

To 1.404 g of sodium hydride (from 2.87 g of a 50% dispersion), under nitrogen, is added 120 ml of sieve-dried dimethylsulfoxide. The mixture is stirred in an 80°-85° C. bath for 35 minutes, then cooled to room temperature. A solution of 14.0 g of the free base 4-(3-fluorobenzylthio)-4-(2-fluorophenyl)-1-methylpiperidine of Example 55a in 47 ml of DMSO is added over 60 seconds and the solution stirred for one hour. The reaction is then poured into 700 ml of ice water and extracted with three 200 ml portions of dichloromethane. The combined dichloromethane extracts are washed with three 300 ml portions of water and one 75 ml portion of saturated sodium chloride solution, and dried over magnesium sulfate to an oil. The oil is chromatographed on alumina with ether to give crystals. A portion of this, in ether is treated with ethereal maleic acid. The resulting salt is washed with ether and dried to give a powder of 3-(3-fluorophenyl)-1,3-dihydro-1'-methylspiro[benzo(c)thiophene-1,4'-piperidine] maleate, m.p. 137°-140° C. A twice recrystallized portion melts at 138.5°-140.5° C. [Upon continued heating, a new crystalline form develops which collapses in the 175°-180° C. range.

Workup

  1. stirringthe solution stirred for one hour
  2. extractionextracted with three 200 ml portions of dichloromethane
  3. washThe combined dichloromethane extracts are washed with three 300 ml portions of water and one 75 ml portion of saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate to an oil
  5. customThe oil is chromatographed on alumina with ether
  6. customto give crystals
  7. washThe resulting salt is washed with ether
  8. customdried

Sources & evidence

ORD record
ord-5f1b749d9d18434ab336fd41a5438cfd
Source dataset
uspto-grants-1983_10
Patent number
US04409229

Reaction notes

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