Binap, (A+-)- → tert-Butyl (1S,4S)-5-(2-methyl-3-pyridyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

HRID 1775341Notes

Reaction equation

Br[C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[C@@H:9]12[CH2:15][C@@H:12]([CH2:13][NH:14]1)[N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10]2.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.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]>[CH3:8][C:3]1[C:2]([N:14]2[CH2:13][C@@H:12]3[CH2:15][C@H:9]2[CH2:10][N:11]3[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-Bromo-2-methylpyridine (258 mg, 1.5 mmol), tert-butyl (1S,4S)-3,6-diazabicyclo[2.2.1]heptane-3-carboxylate (397 mg, 2 mmol), Pd2(DBA)3 (30 mg, 0.033 mmol), sodium tert-butoxide (160 mg, 1.66 mmol), BINAP (60 mg, 0.096 mmol) were placed in anhydrous THF (5 ml), purged with argon and heated under microwave heating at 80° C. in a closed vial for 40 minutes. The mixture was filtered through kieselguhr, concentrated under reduced pressure and purified by column chromatography (silica, gradient from 0 to 50% ethyl acetate in DCM) to yield 230 mg of an orange solid (0.80 mmol, yield 53%). MS (ESI) m/z=290.1 [M+1]+.

Workup

custompurged with argon
temperatureheated under microwave
filtrationThe mixture was filtered through kieselguhr
concentrationconcentrated under reduced pressure
custompurified by column chromatography (silica, gradient from 0 to 50% ethyl acetate in DCM)

Sources & evidence

ORD record: ord-0efa86640ea24102bb456479b140cbab
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260441B2

Reaction notes

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