(3R,5S)-5-(Hydroxymethyl)pyrrolidin-3-OL → (2S,4R)-[6-(4-Hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-methyl-carbamic acid tert-butyl ester

HRID 1951689Notes

Reaction equation

[C:1]([O:5][C:6](=[O:17])[N:7]([C:9]1[CH:10]=[N:11][C:12](Cl)=[CH:13][C:14]=1[I:15])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[OH:18][CH2:19][C@@H:20]1[CH2:24][C@@H:23]([OH:25])[CH2:22][NH:21]1>CS(C)=O>[C:1]([O:5][C:6](=[O:17])[N:7]([C:9]1[CH:10]=[N:11][C:12]([N:21]2[CH2:22][C@H:23]([OH:25])[CH2:24][C@H:20]2[CH2:19][OH:18])=[CH:13][C:14]=1[I:15])[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 26.5 g (71.8 mmol) (6-chloro-4-iodo-pyridin-3-yl)-methyl-carbamic acid tert-butyl ester and 25.4 g (144 mmol) (2S,4R)-2-(hydroxymethyl)-4-hydroxypyrrolidine in 260 ml dimethyl sulfoxide was stirred at 130° C. for 32 h. The reaction mixture was concentrated in vacuo, treated with 200 ml 2 N sodium carbonate solution and extracted with three 200-ml portions of ethyl acetate. The organic layers were washed with 200 ml 2 N sodium carbonate solution and 200 ml brine and dried over sodium sulfate. Flash chromatography gave 15.5 g (48%) of the title compound as a white foam.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additiontreated with 200 ml 2 N sodium carbonate solution
extractionextracted with three 200-ml portions of ethyl acetate
washThe organic layers were washed with 200 ml 2 N sodium carbonate solution and 200 ml brine
dry with materialdried over sodium sulfate

Sources & evidence

ORD record: ord-8a2cbd87c4d843dcb55d5a427ac13ca0
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404708B2

Reaction notes

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