Water → 4-[4-(1-Pyrrolidinyl)butoxy]phenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone Dioxalate Hydrate

HRID 1387082Notes

Reaction equation

HRID 1387082 reaction equation
[H-].[Na+].[N:3]1([CH2:8][CH2:9][CH2:10][CH2:11][OH:12])[CH2:7][CH2:6][CH2:5][CH2:4]1.[N:13]1([CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[S:31][C:30]4[CH:32]=[CH:33][CH:34]=[CH:35][C:29]=4[C:28]=3[C:36]([C:38]3[CH:43]=[CH:42][C:41](F)=[CH:40][CH:39]=3)=[O:37])=[CH:23][CH:22]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1.[OH2:45].CN([CH:49]=[O:50])C>>[OH2:12].[C:49]([OH:50])(=[O:20])[C:11]([OH:12])=[O:45].[C:49]([OH:50])(=[O:12])[C:19]([OH:20])=[O:45].[N:13]1([CH2:18][CH2:19][O:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[S:31][C:30]4[CH:32]=[CH:33][CH:34]=[CH:35][C:29]=4[C:28]=3[C:36]([C:38]3[CH:43]=[CH:42][C:41]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][N:3]4[CH2:7][CH2:6][CH2:5][CH2:4]4)=[CH:40][CH:39]=3)=[O:37])=[CH:25][CH:26]=2)[CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 107182054-Fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketoneHCID 131719524-(Pyrrolidin-1-yl)butan-1-ol

Product 1

HCID 211827494-[4-(1-Pyrrolidinyl)butoxy]phenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone Dioxalate HydrateYield 66%

Procedure

Sodium hydride (49 mg of 60% NaH in mineral oil; 1.23 mmol) was suspended in 3 mL of dry DMF in a flame-dried, argon-filled flask. After stirring for 15 min, a solution of 4-(1-pyrrolidinyl)butanol (Part B) in 1 mL of dry DMF was added. After stirring for 15 min and gas evolution had ceased, 4-fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxyl]phenyl]benzo[b]thiophen-3-yl ketone (Part A) (0.2 g; 0.49 mmol) in 1 mL of dry DMF was added. The mixture was stirred at room temperature for 5 h, then poured into 25 mL of water. Extraction was carried out with Etoac (4×25 mL). The combined organics were washed with brine and dried by passage through sodium sulfate. The title compound (0.18 g; 66% yield) was isolated as a colorless oil by flash chromatography on silica gel, eluting with a gradient of EtOAc(100-85%)/Et3N(0-5%)/MeOH(0-10%). Conversion to the dioxalate was effected as in Example 137, Part E.

Workup

  1. additionfilled flask
  2. stirringAfter stirring for 15 min
  3. stirringThe mixture was stirred at room temperature for 5 h
  4. extractionExtraction
  5. washThe combined organics were washed with brine
  6. dry with materialdried by passage through sodium sulfate

Sources & evidence

ORD record
ord-aabd27c1d7c540e3805784ab257db96b
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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