Potassium Iodide → Cis-4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}-2-[2-(methylthio)ethoxy]benzamide monohydrate

HRID 1086051Notes

Reaction equation

HRID 1086051 reaction equation
[NH2:1][C:2]1[C:29]([Cl:30])=[CH:28][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:11][C@H:10]2[O:26][CH3:27])=[O:7])=[C:4]([OH:31])[CH:3]=1.[H-].[Na+].[CH3:34][S:35][CH2:36][CH2:37]Cl.[I-].[K+]>C(#N)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH2:7].[NH2:1][C:2]1[C:29]([Cl:30])=[CH:28][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH2:11][C@H:10]2[O:26][CH3:27])=[O:7])=[C:4]([O:31][CH2:37][CH2:36][S:35][CH3:34])[CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 109652-Chloroethyl methyl sulfideHCID 24758Sodium hydrideHCID 14372589Cis-4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-hydroxybenzamide

Product 1

HCID 67926058Cis-4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}-2-[2-(methylthio)ethoxy]benzamide monohydrateYield 95.6%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

The product from Step A (0.45 g, 1 mmole) was added to a stirred suspension of sodium hydride (40 mg, 1 mmole of 60%, washed with petroleum ether) in acetonitrile (10 ml) followed by tetrabutylammonium bromide (0.32 g, 1 mmole). The reaction mixture was heated to 40° C. for 15 minutes, and there was then added 2-chloro-ethyl methyl sulfide (0.44 g, 4 mmole) and potassium iodide (50 mg). The mixture was heated to reflux for 2 hours. The solvent was evaporated and the residue was partitioned between ethyl acetate (containing 10% of methylene chloride) and water. The organic layer was dried and the solvent evaporated to leave a residue. The residue was crystallized from 2-propanol to yield 0.26 g (50%) of the title compound, mp. 58°-60° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between ethyl acetate (containing 10% of methylene chloride) and water
  5. customThe organic layer was dried
  6. customthe solvent evaporated
  7. customto leave a residue
  8. customThe residue was crystallized from 2-propanol

Sources & evidence

ORD record
ord-c2c80af80a8e4810a7c8872a463fe65d
Source dataset
uspto-grants-1991_04
Patent number
US05011992

Reaction notes

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