Cesium carbonate → 2-((1S,2R)-2-(1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol

HRID 1474729Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([C@H:7]2[CH2:9][C@H:8]2[CH2:10][CH2:11][OH:12])[CH2:3][CH2:2]1.Cl[C:14]1[N:19]=[CH:18][C:17]([O:20][CH2:21][CH3:22])=[CH:16][N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.CCOC(C)=O.O>[CH2:21]([O:20][C:17]1[CH:16]=[N:15][C:14]([N:1]2[CH2:6][CH2:5][CH:4]([C@H:7]3[CH2:9][C@H:8]3[CH2:10][CH2:11][OH:12])[CH2:3][CH2:2]2)=[N:19][CH:18]=1)[CH3:22]

Participants

Conditions

Temperature: 105 °C

Procedure

2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethanol (4.0 g, 23.6 mmol) and 2-chloro-5-ethoxypyrimidine (4.12 g, 26.0 mmol) were dissolved in 40 mL of DMA, to which was added cesium carbonate (10.0 g, 30.7 mmol). The reaction was heated at 105° C. overnight. The reaction mixture was cooled to rt and diluted with 40 mL of EtOAc and 40 mL of water. The layers were separated and the aqueous phase extracted with EtOAc (30 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (KP-Sil 340 g SNAP column, Biotage system) eluting with 15-80% EtOAc:hexanes over 11 CV to afford the title compound. LC/MS (m/z): 292 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to rt
customThe layers were separated
extractionthe aqueous phase extracted with EtOAc (30 mL×2)
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (KP-Sil 340 g SNAP column, Biotage system)
washeluting with 15-80% EtOAc

Sources & evidence

ORD record: ord-c2a42dab934a4d45a1006c6b4f33cc3d
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018224B2

Reaction notes

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