Dimethylformamide → 1-(2-(3-carboethoxypropyloxy)-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine

HRID 323368Notes

Reaction equation

[OH:1][C:2]1[CH:23]=[CH:22][C:21]([N:24]2[CH:28]=[N:27][N:26]=[N:25]2)=[CH:20][C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([CH2:11][CH2:12][OH:13])[CH2:7]1)=[O:5].CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][CH2:42][CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45]>C(OCC)(=O)C.CO.ClCCl>[C:44]([CH2:43][CH2:42][CH2:41][O:1][C:2]1[CH:23]=[CH:22][C:21]([N:24]2[CH:28]=[N:27][N:26]=[N:25]2)=[CH:20][C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][C:8]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)([CH2:11][CH2:12][OH:13])[CH2:7]1)=[O:5])([O:46][CH2:47][CH3:48])=[O:45]

Participants

Conditions

Temperature: 100 °C

Procedure

Combine 1-(2-hydroxy-5-(1H-tetrazol-1-yl)benzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (0.19 g, 0.5 mmol) and dimethylformamide (5 mL). Add potassium carbonate (82 mg, 0.6 mmol) and 1-bromo-3-carboethoxypropane (0.21 mL, 0.29 g, 1.5 mmol). Heat at 100° C. After 2.5 hours, cool to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate, extract with water, aqueous 1 M hydrochloric acid solution, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia to give the title compound: Rf=0.28 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).

Workup

temperaturecool to ambient temperature
waitAfter 18 hours
extractionextract with water, aqueous 1 M hydrochloric acid solution
dry with materialDry the organic layer over Na2SO4
filtrationfilter
customevaporate in vacuo
customto give a residue

Sources & evidence

ORD record: ord-19cba9a5a08643718923538aedf12b45
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06211199B1

Reaction notes

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