Cesium carbonate → HCID 178484153, compound

HRID 1159377Notes

Reaction equation

HRID 1159377 reaction equation
NC[C@@H]1C[C@H](O)C1.CS([O:12][C@H:13]1[CH2:16][C@@H:15]([CH2:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH3:19])[CH2:14]1)(=O)=O.[F:27][C:28]1[CH:29]=[C:30](O)[CH:31]=[C:32]([F:40])[C:33]=1[CH2:34][N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.CCOC(C)=O.O>[F:27][C:28]1[CH:29]=[C:30]([CH:31]=[C:32]([F:40])[C:33]=1[CH2:34][N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1)[O:12][C@H:13]1[CH2:16][C@H:15]([CH2:17][N:18]([CH3:19])[C:20](=[O:21])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:14]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 686181603,5-Difluoro-4-(pyrrolidin-1-ylmethyl)phenolHCID 178484154HCID 178484154, compoundHCID 178511298HCID 178511298, compound

Product 1

HCID 178484153HCID 178484153, compoundYield 98.9%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
92.5 °C

Procedure

A mixture of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)-amino]methyl}cyclobutyl methanesulfonate (2 g, 6.9 mmol), intermediate 21, 3,5-difluoro-4-(pyrrolidin-1-ylmethyl)phenol (3.47 g, 13.8 mmol) and Cs2CO3 (4.5 g, 13.8 mmol) in DMSO (20 mL) was heated at 90-95° C. for 4 h under vigorous stirring in a flow of argon, then cooled. Water (40 ml) and EtOAc (40 ml) were added, and the layers were separated. The water layer was extracted with ether (20 ml), the combined organic layers were washed with 1N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated to give the title compound (2.8 g, 98%) as a yellow oil. LC/MS data: 411.6, 412.6 (M+H) (calculated for C22H32F2N2O3 410.51). 1H NMR-data (DMSO-d6): 6.50-6.61 (m, 2H, Ar—H); 4.79-4.87 (m, 1H); 3.55 (s, 2H, CH2); 3.32 (d, 2H, J=8.1 Hz, CH2); 2.78 (s, 3H, NCH3); 2.52-2.62 (m, 1H); 2.38-2.50 (m, 4H); 2.20-2.28 (m, 2H); 2.05-2.17 (m, 2H); 1.58-1.73 (m, 4H); 1.41 (s, 9H, Boc).

Workup

  1. temperaturecooled
  2. customthe layers were separated
  3. extractionThe water layer was extracted with ether (20 ml)
  4. washthe combined organic layers were washed with 1N NaOH (3×25 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-a209546f3ce34e5abf79ff66428371f5
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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