2-Methylpyridine → [(R)-1-(2-Fluoro-benzyl)-2-oxo-3-pyridin-2-yl-propyl]-carbamic acid tert-butyl ester

HRID 1094466Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:7].C([Li])CCC.[C:13]([O:17][C:18](=[O:35])[NH:19][C@@H:20]([C:29](=[O:34])N(OC)C)[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])([CH3:16])([CH3:15])[CH3:14].OS([O-])(=O)=O.[Na+]>C1COCC1.O>[C:13]([O:17][C:18](=[O:35])[NH:19][C@H:20]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])[C:29](=[O:34])[CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 15 °C

Procedure

To a solution of 2-picoline (0.54 mL, 5.5 mmol) in 20 mL of THF at −52° C. is slowly added a 1.5 M solution of n-butyllithium in hexanes (3.6 mL, 5.5 mmol). The reaction is then warmed to 15° C. and is then immediately re-cooled to −52° C. To the reaction is added a solution of [(R)-2-(2-fluoro-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (0.6 g, 1.8 mmol) in 4 mL of THF. The reaction is then is poured into 8 mL of a 2M solution of NaHSO4 in water. The solution is adjusted to pH7 by addition of pH7 buffer and the product is extracted into ether. The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the title compound.

Workup

temperatureis then immediately re-cooled to −52° C
additionThe solution is adjusted to pH7 by addition of pH7 buffer
extractionthe product is extracted into ether
dry with materialThe organic phase is dried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-93bc6102a41540499e301a8e7fdf768a
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08133907B2

Reaction notes

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