2,2,2-Trifluoroethanol → HCID 67269737, compound

HRID 1697233Notes

Reaction equation

HRID 1697233 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:33][C:34](=[O:38])[CH2:35][O:36][CH3:37])[C@H:10]([OH:32])[CH2:11][NH:12][C@@H:13]2[C:22]3[C:17](=[C:18](Cl)[N:19]=[C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:21]=3)[O:16][C:15]3([CH2:31][CH2:30][CH2:29]3)[CH2:14]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.[F:73][C:74]([F:78])([F:77])[CH2:75][OH:76]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:20]1[CH:21]=[C:22]2[C@@H:13]([NH:12][CH2:11][C@@H:10]([OH:32])[C@@H:9]([NH:33][C:34](=[O:38])[CH2:35][O:36][CH3:37])[CH2:8][C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH2:14][C:15]3([CH2:31][CH2:30][CH2:29]3)[O:16][C:17]2=[C:18]([O:76][CH2:75][C:74]([F:78])([F:77])[F:73])[N:19]=1

Participants

7

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86635709HCID 86635709, compound

Product 1

HCID 67269737HCID 67269737, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a flame-dried microwave vial under Ar gas was added N-((1S,2R)-1-((3-fluorophenyl)methyl)-3-(((4′S)-8′-chloro-6′-(2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-c]pyridin]-4′-yl)amino)-2-hydroxypropyl)-2-(methyloxy)acetamide (100 mg, 182 μmol), cesium carbonate (357 mg, 1095 μmol), DavePhos (79 mg, 201 μmol), palladium(II) acetate (41 mg, 182 μmol) were added and vial was flushed with N2 5×, then 2,2,2-trifluoroethanol (332 μl, 4561 μmol) and toluene (1 mL) were added simultaneously. The reaction was heated in the microwave at 110° C. for 30 min. The reaction mixture was filtered through a small plug of silica gel, and the residue purified by reverse phase HPLC to give the title compound as a tan amorphous solid. MS m/z: 612.0 (M+1).

Workup

  1. additionwere added
  2. customvial was flushed with N2 5×
  3. filtrationThe reaction mixture was filtered through a small plug of silica gel
  4. customthe residue purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5dea0267f78e4c198cace526ca5db631
Source dataset
uspto-grants-2012_04
Patent number
US08163909B2

Reaction notes

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