Cesium fluoride → HCID 58203867, compound

HRID 708266Notes

Reaction equation

HRID 708266 reaction equation
CC1(C)COB([C:8]2[CH:29]=[CH:28][C:11]3[C:12]4[N:13]=[C:14]([C:20]5[N:21]([CH:25]([CH3:27])[CH3:26])[N:22]=[CH:23][N:24]=5)[S:15][C:16]=4[CH2:17][CH2:18][O:19][C:10]=3[CH:9]=2)OC1.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41](=[O:44])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C.[F-].[Cs+]>C1CC=CCCC=C1.C1CC=CCCC=C1.[Ni]>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]([OH:44])([C:8]2[CH:29]=[CH:28][C:11]3[C:12]4[N:13]=[C:14]([C:20]5[N:21]([CH:25]([CH3:26])[CH3:27])[N:22]=[CH:23][N:24]=5)[S:15][C:16]=4[CH2:17][CH2:18][O:19][C:10]=3[CH:9]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27349131,3-Bis(2,6-diisopropylphenyl)imidazolium chlorideHCID 58203944HCID 58203944, compound

Product 1

HCID 58203867HCID 58203867, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6433264Bis(1,5-cyclooctadiene)nickelCatalyst

Conditions

Temperature
80 °C

Procedure

8-(5,5-Dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (200 mg, 0.47 mmol), 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (63 mg, 0.31 mmol), bis(1,5-cyclooctadiene)nickel(0) (17 mg, 0.063 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (27 mg, 0.063 mmol) and cesium fluoride (81 mg, 0.53 mmol) were loaded into a reaction vial, which was then flushed with nitrogen. Dry toluene (3 mL) was then added and nitrogen was bubbled through the mixture for 15 min. before heating at 80° C. for 30 min. The reaction mixture was combined with a mixture from a similar reaction (same quantities of boronate ester and oxo-piperidine, half-quantities of nickel and imidazolium catalysts, heated for 19.5 h) and extracted with ethyl acetate. The organic extract was washed with saturated aqueous sodium bicarbonate followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 20-70% ethyl acetate in cyclohexane) to give 4-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (100 mg). LCMS RT=4.73, [M+H]+=512.

Workup

  1. customwhich was then flushed with nitrogen
  2. additionDry toluene (3 mL) was then added
  3. customnitrogen was bubbled through the mixture for 15 min.
  4. customThe reaction mixture was combined with a mixture from a similar reaction (same quantities of boronate ester and oxo-piperidine, half-quantities of nickel and imidazolium catalysts, heated for 19.5 h)
  5. extractionextracted with ethyl acetate
  6. extractionThe organic extract
  7. washwas washed with saturated aqueous sodium bicarbonate
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0f5879ab9154fd3b3f67504726894b7
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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