Cesium carbonate → HCID 178484152, compound

HRID 1159374Notes

Reaction equation

HRID 1159374 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.[Cl: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>[Cl: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 686192543-Chloro-5-fluoro-4-(pyrrolidin-1-ylmethyl)phenolHCID 178484154HCID 178484154, compoundHCID 178511298HCID 178511298, compound

Product 1

HCID 178484152HCID 178484152, compoundYield 82%

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 (1.5 g, 5.2 mmol), intermediate 18, 3-chloro-5-fluoro-4-(pyrrolidin-1-ylmethyl)phenol (2.38 g, 10.4 mmol) and Cs2CO3 (3.38 g, 10.4 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 (1.8 g, 82%) as a yellow oil. LC/MS data: 427.6, 429.6, 430.5 (M+H) (calculated for C22H32CFIN2O3 426.96). 1H NMR-data (DMSO-d6): 6.76 (br. s, 1H, Ar—H); 6.71 (dd, 1H, J1=2.2 Hz, J2=11.5 Hz, Ar—H); 4.79-4.92 (m, 1H); 3.65 (s, 2H); 3.32 (d, 2H, J=8.0 Hz); 2.78 (s, 3H, NCH3); 2.38-2.62 (m, 5H+DMSO); 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-26d7f791961441ea9217c523ab2c9b24
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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