Cesium carbonate → HCID 178484145, compound

HRID 1159379Notes

Reaction equation

HRID 1159379 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[C:33]([CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[C:32]([Cl:40])[CH:31]=[CH:30][C:29]=1O.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.CCOCC.O>[Cl:40][C:32]1[C:33]([CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[C:28]([Cl:27])[CH:29]=[CH:30][C:31]=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 686208052,4-Dichloro-3-(pyrrolidin-1-ylmethyl)phenolHCID 178484154HCID 178484154, compoundHCID 178511298HCID 178511298, compound

Product 1

HCID 178484145HCID 178484145, compoundYield 70.7%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
92.5 °C

Procedure

To a mixture of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)amino]-methyl}cyclobutyl methanesulfonate (1.59 g, 5.42 mmol), intermediate 23, 2,4-dichloro-3-(pyrrolidin-1-ylmethyl)phenol (2 g, 8.13 mmol), and Cs2CO3 (2.65 g, 8.13 mmol) in DMSO (30 mL) was heated at 90-95° C. for 2 h under vigorous stirring in a flow of argon, and then cooled. Water (20 mL) and ether (50 mL) were added, and the layers were separated. The water layer was subjected to extraction with ether (2×50 mL). The combined organic layers were washed with water (30 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0→80:20) to furnish the title compound (1.7 g, 70%). LC/MS data: 443.1, 444.1, 445.1 (M+H) (calculated for C22H32Cl2N2O3 443.42). 1H NMR-data (DMSO-d6): 7.35 (d, 1H, J=9 Hz, Ar—H); 6.86 (d, 1H, J=9 Hz, Ar—H); 4.81-4.90 (m, 1H); 3.82 (brs, 2H, CH2); 3.33 (d, 2H, J=8 Hz, CH2); 2.78 (s, 3H, NCH3); 2.50-2.62 (m, 5H); 2.22-2.30 (m, 2H); 2.11-2.21 (m, 2H), 1.58-1.72 (m, 4H); 1.40 (brs, 9H, Boc).

Workup

  1. temperaturecooled
  2. customthe layers were separated
  3. extractionThe water layer was subjected to extraction with ether (2×50 mL)
  4. washThe combined organic layers were washed with water (30 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0→80:20)

Sources & evidence

ORD record
ord-3e41b21d2a0e4fcf9d96d31683dca990
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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