Sodium hydride → Benzyl 3-(2-benzyloxyethoxy)pyrrolidine-1-carboxylate

HRID 467520

Reaction equation

[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.[H-].[Na+].Br[CH2:20][CH2:21][O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:23]([O:22][CH2:21][CH2:20][O:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 1.29 g of benzyl 3-hydroxypyrrolidine-1-carboxylate in 80 ml of THF is cooled to 0° C., 0.245 g of 60% NaH in oil is added and then 1.26 g of [(2-bromoethoxy)methyl]benzene and 0.108 g of tetrabutylammonium iodide and it is heated at 80° C. for 3 hours. 0.28 g of NaH and 0.40 g of [(2-bromoethoxy)methyl]benzene are added and it is heated at 80° C. for 2 hours. The reaction mixture is concentrated under vacuum, the residue is extracted with DCM, the organic phase is washed with 0.1M HCl solution, with a saturated solution of NaHCO3, it is dried and the solvent is evaporated under vacuum. The product thus obtained is purified by preparative HPLC and 0.46 g of the expected compound is obtained.

Workup

concentrationThe reaction mixture is concentrated under vacuum
extractionthe residue is extracted with DCM
washthe organic phase is washed with 0.1M HCl solution, with a saturated solution of NaHCO3, it
customis dried
customthe solvent is evaporated under vacuum
customThe product thus obtained
customis purified by preparative HPLC

Sources & evidence

ORD record: ord-31c6ebefc897422a9c8ff8c9e97cc707
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623862B2

Linked notes

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