Cesium carbonate → HCID 66969218, compound

HRID 1255529Notes

Reaction equation

HRID 1255529 reaction equation
Br[C:2]1[C:27](=[O:28])[N:26]2[C:5]([O:6][C@H:7]3[CH2:36][N:10]([C:11](=[O:35])[C@H:12]([CH:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)[NH:13][C:14](=[O:29])[O:15][C@H:16]4[C@H:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[CH2:19][CH2:18][CH2:17]4)[C@H:9]([C:37]([O:39][CH3:40])=[O:38])[CH2:8]3)=[CH:4][CH:3]=1.[C:41]1(B(O)O)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.S(=O)(=O)(O)[O-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:30]1([C@H:12]2[C:11](=[O:35])[N:10]3[CH2:36][C@@H:7]([CH2:8][C@H:9]3[C:37]([O:39][CH3:40])=[O:38])[O:6][C:5]3[N:26]([C:27](=[O:28])[C:2]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:3][CH:4]=3)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]3[C@@H:16]([CH2:17][CH2:18][CH2:19]3)[O:15][C:14](=[O:29])[NH:13]2)[CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 75806TricyclohexylphosphineHCID 516920Potassium bisulfateHCID 66968760HCID 66968760, compound

Product 1

HCID 66969218HCID 66969218, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

An oven-dried 100 mL Kjeldahl Flask under nitrogen was charged with the product of Example 83 Step 1 (100 mg, 0.161 mmol), dioxane (5 ml), phenylboronic acid (24.48 mg, 0.201 mmol), cesium carbonate (65.4 mg, 0.201 mmol), tricyclohexylphosphine (13.51 mg, 0.048 mmol), and tris(dibenzylideneacetone)dipalladium(0) (17.65 mg, 0.019 mmol). Heated in an 80° C. oil bath for 20 hours. HPLC/MS looks good. Cooled. Poured into 2.5% potassium bisulfate. Extracted three times with ethyl acetate, washed combined organic portions with brine, dried with anhydrous magnesium sulfate, filtered and rotary evaporated filtrate. Subjected to ISCO chromatography eluting with a hexane/ethyl acetate gradient. Evaporation of fractions containing product gave the title compound as a white solid remained. (75 mg, 0.121 mmol, 75% yield). LCMS (ES+) m/z 620.3 (M+H)+.

Workup

  1. temperatureCooled
  2. extractionExtracted three times with ethyl acetate
  3. washwashed
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. washeluting with a hexane/ethyl acetate gradient
  7. customEvaporation of fractions
  8. additioncontaining product

Sources & evidence

ORD record
ord-263b0726f66d472eb68310aea5516eab
Source dataset
uspto-grants-2013_06
Patent number
US08461107B2

Reaction notes

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