3-Bromo-5-methylpyridine → (R)-tert-butyl 3-((4-methylpyridin-2-yl)amino)piperidine-1-carboxylate

HRID 1775338Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6](C)[CH:7]=1.[CH3:9]C(C)([O-])C.[Na+].[NH2:15][C@@H:16]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C>[CH3:9][C:7]1[CH:2]=[CH:3][N:4]=[C:5]([NH:15][C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]2)[CH:6]=1

Participants

Conditions

Temperature: 70 °C

Procedure

3-Bromo-5-methylpyridine (200 mg, 1.163 mmol), sodium tert-butoxide (223 mg, 2.325 mmol), tert-butyl (3R)-3-aminopiperidine-1-carboxylate (349 mg, 1.744 mmol) and BrettPhos (31.2 mg, 0.058 mmol) in anhydrous dioxane (10 ml) was purged with argon. Pd2(DBA)3 (53.2 mg, 0.058 mmol) was added and the mixture was stirred at 70° C. for two hours. After cooling to room temperature the mixture was filtered through kieselguhr, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica, gradient from 0.5 to 10% methanol containing 7N NH3 in DCM) to yield 271 mg of an orange solid (0.93 mmol, 64%) MS (ESI) m/z=292.2 [M+1]+.

Workup

temperatureAfter cooling to room temperature the mixture
filtrationwas filtered through kieselguhr
concentrationthe filtrate was concentrated under reduced pressure
customthe residue was purified by column chromatography (silica, gradient from 0.5 to 10% methanol containing 7N NH3 in DCM)

Sources & evidence

ORD record: ord-f6c70b95df2e4aae857d4835ec7edd4f
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260441B2

Reaction notes

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