Potassium Carbonate → HCID 67408859, compound

HRID 340802Notes

Reaction equation

HRID 340802 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:12][CH:11]=2)=[O:9])[CH2:4][CH2:3]1.[C:25]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:30]=[CH:29][C:28]([CH2:31][N:32]2[C:36]3[CH:37]=[C:38]([F:49])[C:39]([C:42]4[CH:47]=[CH:46][C:45](Br)=[CH:44][CH:43]=4)=[C:40]([F:41])[C:35]=3[N:34]=[C:33]2[O:50][CH:51]2[CH2:56][CH2:55][CH:54]([C:57]([O:59][CH2:60][CH3:61])=[O:58])[CH2:53][CH2:52]2)=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:25]1([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:26]=[CH:27][C:28]([CH2:31][N:32]2[C:36]3[CH:37]=[C:38]([F:49])[C:39]([C:42]4[CH:43]=[CH:44][C:45]([C:13]5[CH:12]=[CH:11][C:10]([C:8]([N:5]6[CH2:4][CH2:3][CH:2]([OH:1])[CH2:7][CH2:6]6)=[O:9])=[CH:15][CH:14]=5)=[CH:46][CH:47]=4)=[C:40]([F:41])[C:35]=3[N:34]=[C:33]2[O:50][CH:51]2[CH2:52][CH2:53][CH:54]([C:57]([O:59][CH2:60][CH3:61])=[O:58])[CH2:55][CH2:56]2)=[CH:29][CH:30]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 67388407HCID 67388407, compoundHCID 67406385HCID 67406385, compound

Product 1

HCID 67408859HCID 67408859, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a yellow solution of (4-hydroxypiperidin-1-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone (0.147 g, 0.443 mmol), ethyl 4-{[1-(biphenyl-4-ylmethyl)-5-(4-bromophenyl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclohexane-carboxylate (0.260 g, 0.403 mmol), and Pd(PPh3)4 (0.028 g, 0.024 mmol) was added 1 M K2CO3 (1.20 mL, 1.20 mmol) dropwise via syringe. The mixture was heated at 120° C. for 45 min, and then diluted with EtOAc and H2O. The aqueous layer was separated and further extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification of the resulting residue by flash chromatography (100% EtOAc) afforded the desired compound as a ˜2:1 mixture of trans/cis isomers. The cis/trans isomers were separated via reverse phase Gilson™ HPLC (60-100% MeCN/H2O) to afford a faster eluting isomer A and a slower eluting isomer B as white solids.

Workup

  1. customThe aqueous layer was separated
  2. extractionfurther extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the resulting residue by flash chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-398281e268c7453e925717a4b3bdbf4d
Source dataset
uspto-grants-2014_11
Patent number
US08895596B2

Reaction notes

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