Cesium carbonate → tert-butyl 3-(2-chloropyrimidin-4-yloxy)azetidine-1-carboxylate

HRID 410627Notes

Reaction equation

HRID 410627 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[OH:9][CH:10]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([O:9][CH:10]2[CH2:11][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 775312,4-DichloropyrimidineHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylate

Product 1

HCID 77231488tert-butyl 3-(2-chloropyrimidin-4-yloxy)azetidine-1-carboxylateYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A flask was charged with a solution of 2,4-dichloropyrimidine (300 mg, 2.0 mmol) in N,N′-dimethylformamide (10 mL). tert-Butyl 3-hydroxyazetidine-1-carboxylate (349 mg, 2.0 mmol) and cesium carbonate (1.11 g, 3.42 mmol) were added and the resulting mixture was heated to 80° C. for 2 h. Upon completion, the mixture was diluted with ethyl acetate (20 mL) and washed with 1:1 water:brine (3×40 mL). The organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by Chromatography on silica gel (0-80% ethyl acetate in hexanes) afforded tert-butyl 3-[(2-chloropyrimidin-4-yl)oxy]azetidine-1-carboxylate (550 mg, 1.9 mmol, 96%). MS EST: [M+H]+ m/z 286.1.

Workup

  1. washwashed with 1:1 water
  2. dry with materialThe organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by Chromatography on silica gel (0-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e8b4386ef60a464eb9c87567665d9135
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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