Cesium carbonate → 2-(2-{4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidin-1-yl}pyrimidin-5-yl)propan-2-ol

HRID 1474707Notes

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]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.O>[OH:12][CH2:11][CH2:10][C@@H:8]1[CH2:9][C@@H:7]1[CH:4]1[CH2:5][CH2:6][N:1]([C:14]2[N:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][N:15]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 65 °C

Procedure

2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethanol (810 mg, 4.79 mmol) and 2-(2-chloropyrimidin-5-yl)propan-2-ol (991 mg, 5.74 mmol) were dissolved in 12 mL of DMF, to which was added cesium carbonate (2.0 g, 6.20 mmol). The mixture was heated at 65° C. overnight. The mixture was cooled to rt, diluted with 20 mL of EtOAc and 20 mL of water. The layers were separated and the aqueous phase extracted with EtOAc (20 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 50 SNAP column, Biotage system) eluting with a range of 40-90% EtOAc/Hex over 12 CV to give the desired compound. LC/MS (m/z): 306 (M+H)+.

Workup

temperatureThe mixture was cooled to rt
customThe layers were separated
extractionthe aqueous phase extracted with EtOAc (20 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 50 SNAP column, Biotage system)
washeluting with a range of 40-90% EtOAc/Hex over 12 CV

Sources & evidence

ORD record: ord-b304e65522f74cfa9804b1e39fd693c5
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018224B2

Reaction notes

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