Cesium carbonate → HCID 86722480, compound

HRID 718863Notes

Reaction equation

HRID 718863 reaction equation
FC(F)(F)S(O[C:7]1[N:12]=[CH:11][C:10]2[C:13]3([CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:25][CH2:24][C:19]4([O:23][CH2:22][CH2:21][O:20]4)[CH2:18][CH:14]3[CH2:15][CH2:16][CH2:17][C:9]=2[CH:8]=1)(=O)=O.[CH:35](/B(O)O)=[CH:36]\[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[N:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[CH2:26][C@@:13]12[CH2:25][CH2:24][C:19]3([O:23][CH2:22][CH2:21][O:20]3)[CH2:18][C@H:14]1[CH2:15][CH2:16][CH2:17][C:9]1[CH:8]=[C:7](/[CH:35]=[CH:36]/[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:12]=[CH:11][C:10]=12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 5702628Styrylboronic acidHCID 86722479HCID 86722479, compound

Product 1

HCID 86722480HCID 86722480, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A flask with stir bar and nitrogen line was charged with rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-yl trifluoromethanesulfonate (144, R2=Pyridin-2-ylmethyl) (9.14 g, 18.34 mmol) (assumed 100% for previous reaction), (E)-styrylboronic acid (3.39 g, 22.9 mmol), cesium carbonate (14.94 g, 45.9 mmol), 1,4-dioxane (130 mL), water (32.5 mL) and bis(triphenylphosphine)palladium(II) dichloride (0.644 g, 0.917 mmol). The mixture was warmed in an oil bath heated to about 90° C. for about 30 min. The mixture was cooled then concentrated under reduced pressure. The material was partitioned between water (100 mL) and EtOAc (100 mL). The layers were separated then the organic solution was washed with brine (75 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The filtrate was concentrated under reduced pressure then the material was purified on silica gel (330 g) using 100% EtOAc. Product fractions were combined and concentrated under reduced pressure to yield (7aR,11aS)-11a-(pyridin-2-ylmethyl)-3-((E)-styryl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane] (145, R2=Pyridin-2-ylmethyl) (6.15 g, 74%); LC/MS, method 3, Rt=2.50 min, MS m/z 453 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.14 (s, 1H), 7.59-7.52 (m, 3H), 7.38-7.35 (m, 2H), 7.33-7.05 (m, 4H), 6.97-6.94 (m, 1H), 6.23 (s, 1H), 4.04-3.90 (m, 4H), 3.49 (d, J=13.8 Hz, 1H), 3.39-3.29 (m, 1H), 3.25 (d, J=13.3 Hz, 1H), 2.97-2.89 (m, 1H), 2.28-2.20 (m, 1H), 2.11-1.96 (m, 4H), 1.92-1.86 (m, 1H), 1.84-1.70 (m, 2H), 1.69-1.48 (m, 3H).

Workup

  1. temperatureThe mixture was warmed in an oil bath
  2. temperatureThe mixture was cooled
  3. concentrationthen concentrated under reduced pressure
  4. customThe material was partitioned between water (100 mL) and EtOAc (100 mL)
  5. customThe layers were separated
  6. washthe organic solution was washed with brine (75 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe material was purified on silica gel (330 g)
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4af4aa2d6b5f47de8c20ee08e5019109
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

Loading…