Cesium carbonate → (1S,6R)-Benzyl 3-(4,6-dimethylpyrimidin-2-yl)-3,8-diazabicyclo[4.2.0]octane-8-carboxylate

HRID 2175009Notes

Reaction equation

[C@H:1]12[N:8]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH2:7][C@H:6]1[CH2:5][CH2:4][NH:3][CH2:2]2.Cl[C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[N:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:27][C:22]1[CH:23]=[C:24]([CH3:26])[N:25]=[C:20]([N:3]2[CH2:4][CH2:5][C@H:6]3[C@H:1]([N:8]([C:9]([O:11][CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:10])[CH2:7]3)[CH2:2]2)[N:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To (1S,6R)-benzyl 3,8-diazabicyclo[4.2.0]octane-8-carboxylate (2.5 g, 6.9 mmol) and 2-chloro-4,6-dimethylpyrimidine (980 mg, 6.9 mmol) in DMF (35 mL) was added Cs2CO3 (9.0 g, 27.6 mmol). The reaction flask was heated to 100° C. until starting materials were consumed, cooled to rt, diluted with EtOAc and washed with H2O. The aqueous layer was back-extracted with EtOAc (1×). The combined organics were washed with brine and dried (Na2SO4) to give an oil. Purification via silica gel (15-75% EtOAc in hexanes) gave 1.6 g (63%) of the title compound as a clear oil. MS (ESI) mass calcd. C20H24N4O2, 352.44; m/z found 353.2 [M+H]+.

Workup

customwere consumed
temperaturecooled to rt
additiondiluted with EtOAc
washwashed with H2O
extractionThe aqueous layer was back-extracted with EtOAc (1×)
washThe combined organics were washed with brine
dry with materialdried (Na2SO4)
customto give an oil
customPurification via silica gel (15-75% EtOAc in hexanes)

Sources & evidence

ORD record: ord-baa397a618374cc5b64482dd3d90fe07
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062044B2

Reaction notes

Loading…