Ethanethiol → 1-[2-[2-Hydroxy-4-[6-hydroxy-3-[3-methyl-4-[(1-pyrrolidinyl)methyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine Dioxalate

HRID 1070327Notes

Reaction equation

HRID 1070327 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:7]([OH:12])(=[O:11])[C:8]([OH:10])=[O:9].[OH:13][C:14]1[CH:15]=[CH:16][C:17]2[C:21]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([CH2:29][N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=[C:25]([CH3:35])[CH:24]=3)=[C:20]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][CH2:44][N:45]4[CH2:49][CH2:48][CH2:47][CH2:46]4)=[C:38]([O:50]C)[CH:37]=3)[S:19][C:18]=2[CH:52]=1.CCS.[Al+3].[Cl-].[Cl-].[Cl-].C([O-])(O)=O.[Na+]>ClCCCl>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:7]([OH:12])(=[O:11])[C:8]([OH:10])=[O:9].[OH:50][C:38]1[CH:37]=[C:36]([C:20]2[S:19][C:18]3[CH:52]=[C:14]([OH:13])[CH:15]=[CH:16][C:17]=3[C:21]=2[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:25]([CH3:35])[CH:24]=2)[CH:41]=[CH:40][C:39]=1[O:42][CH2:43][CH2:44][N:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) ChlorideHCID 86757088HCID 86757088, compound

Product 1

HCID 867570891-[2-[2-Hydroxy-4-[6-hydroxy-3-[3-methyl-4-[(1-pyrrolidinyl)methyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine Dioxalate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 1-[[4-[6-hydroxy-2-[3-methoxy-4-[2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophen-3-yl]methyl-2-methylphenyl]methyl]pyrrolidine (Example 127, Part D; 182 mg, 0.327 mmol) in 5 mL of 1,2-dichloroethane was cooled to 0° C. and treated with EtSH (195 μL, 2.62 mmol) followed by AlCl3 (262 mg, 1.96 mmol). The resulting mixture was allowed to warm to ambient temperature. After 16 h, the reaction mixture was poured into 10 mL of saturated aqueous NaHCO3 solution. The aqueous layer was extracted with 5% MeOH/CHCl3 (3×10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by radial chromatography (SiO2; gradient of 1% to 4% MeOH in CHCl3, saturated with NH4OH) gave 96 mg (0.177 mmol; 54%) of a white foam. Subsequent dioxalate salt formation as described in Example 1, Part C afforded the title compound as a white solid.

Workup

  1. extractionThe aqueous layer was extracted with 5% MeOH/CHCl3 (3×10 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by radial chromatography (SiO2; gradient of 1% to 4% MeOH in CHCl3, saturated with NH4OH)
  6. customgave 96 mg (0.177 mmol; 54%) of a white foam

Sources & evidence

ORD record
ord-654a7d1fffa84fa6869278c0bcccf2a1
Source dataset
uspto-grants-2001_06
Patent number
US06251921B1

Reaction notes

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