2,5-Dibromopyridine → 3-(5-Bromo-pyridine-2-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 423393

Reaction equation

[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH:23]([C:26](=[O:31])N(OC)C)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>C1(C)C=CC=CC=1>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH:23]([C:26]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=2)=[O:31])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: -80 °C

Procedure

Add dropwise n-BuLi (3.2 mL, 5.1 mmol) to an suspension of 2,5-dibromopyridine (1.0 g, 4.2 mmol) in dry toluene (50 mL) at −80° C. under nitrogen. Allow the mixture to stir at −80° C. for 2 h. Slowly add a solution of 3-(methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.4 g, 5.5 mmol) in dry toluene (10 mL). Allow the reaction mixture to stir for 1 h at −78° C., then warm to −10° C. Quench the mixture with saturated NH4Cl (1 mL) and warm to RT. Separate the organic layer and concentrate. Purify the crude material by flash chromatography, eluting with 10-20% ethylacetate/hexane to give 0.61 g (43%) of the title compound. LC-MS/ES m/z (79Br) 299 [M-tert-Bu+H]+.

Workup

stirringto stir for 1 h at −78° C.
temperaturewarm to −10° C
customQuench the mixture with saturated NH4Cl (1 mL)
temperaturewarm to RT
customSeparate the organic layer
concentrationconcentrate
customPurify the crude material by flash chromatography
washeluting with 10-20% ethylacetate/hexane

Sources & evidence

ORD record: ord-43c18ff452f74b25851cdba05be5e396
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101764B2

Linked notes

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