Cesium carbonate → HCID 86602700, compound

HRID 1375010Notes

Reaction equation

HRID 1375010 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28](OS(C(F)(F)F)(=O)=O)[CH:27]=1)=[O:7].[C:50](=[NH:63])([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[F:48][C:2]([F:1])([F:49])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:46])([F:45])[F:47])[CH:43]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([N:63]=[C:50]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH:27]=1)=[O:7]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 56986717HCID 56986717, compound

Product 1

HCID 86602700HCID 86602700, compoundYield 72%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methyl-3-trifluoromethanesulfonyloxybenzyl)-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (0.10 g), benzophenone imine (30.5 mg), cesium carbonate (62 mg), palladium acetate (3 mg), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (12.7 mg) in toluene was stirred at 80° C. under nitrogen atmosphere for 22 hours. After cooling, water and ethyl acetate were added to the mixture and the organic layer was separated, washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (NH-DM1020, Fuji Silysia Chemical Ltd.) with a mixture of hexane and ethyl acetate (3:1) as eluent to give (2R)-1-[3,5-bis(trifluorometh yl)benzoyl]-2-[3-(diphenylmethyleneamino)-4-methylbenzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (75 mg) as an oil.

Workup

  1. temperatureAfter cooling
  2. customthe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (NH-DM1020, Fuji Silysia Chemical Ltd.) with a mixture of hexane and ethyl acetate (3:1) as eluent

Sources & evidence

ORD record
ord-8646a4e67643475d881fc62dbfc178e8
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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