2,6-Lutidine → HCID 86722481, compound

HRID 718864Notes

Reaction equation

HRID 718864 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C@@:8]12[CH2:34][CH2:33][C:28]3([O:32][CH2:31][CH2:30][O:29]3)[CH2:27][C@H:9]1[CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[C:17](/[CH:19]=C/C3C=CC=CC=3)[N:16]=[CH:15][C:14]=12.[O:35]1CCOCC1.CC1C=CC=C(C)N=1.I([O-])(=O)(=O)=O.[Na+]>O.CCOC(C)=O.[Os](=O)(=O)(=O)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]12[CH2:34][CH2:33][C:28]3([O:32][CH2:31][CH2:30][O:29]3)[CH2:27][CH:9]1[CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[C:17]([CH:19]=[O:35])[N:16]=[CH:15][C:14]=12

Participants

8

Reactant 4

HCID 79372,6-LutidineHCID 312751,4-DioxaneHCID 23667635Sodium periodateHCID 86722480HCID 86722480, compound

Product 1

HCID 86722481HCID 86722481, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A flask with stir bar and nitrogen line was charged with rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-3-((E)-styryl)-5,6,7,7a,8,10,11,11a-octahydro spiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane] (145, R2=Pyridin-2-ylmethyl) (5.9 g, 13.04 mmol), 1,4-dioxane (150 mL), water (50.0 mL), 2,6-dimethylpyridine (3.04 mL, 26.1 mmol) and osmium(VIII) oxide (2.5 wt % in tert-butanol) (4.91 mL, 0.391 mmol). Sodium periodate (11.15 g, 52.1 mmol) was added and the mixture was stirred at rt for about 15 h. The mixture was diluted with water (200 mL) and EtOAc (50 mL). The layers were separated then the aqueous layer was extracted four times with EtOAc (50 mL). The combined organics were washed twice with brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The material was triturated with EtOAc and the solids collected by filtration and dried to yield rac-(7aR,11 aR)-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]dioxolane]-3-carbaldehyde (146, R2=Pyridin-2-ylmethyl) (3.89 g, 79%); LC/MS, method 3, Rt=2.00 min, MS m/z 379 (M+H)+. 1H NMR (400 MHz, DMSO) δ 9.87 (s, 1H), 8.29-8.27 (m, 1H), 8.22 (s, 1H), 7.69 (s, 1H), 7.40-7.36 (m, 1H), 7.05-7.02 (m, 1H), 6.41 (d, J=7.8 Hz, 1H), 3.94-3.84 (m, 4H), 3.50 (d, J=13.3 Hz, 1H), 3.44-3.36 (m, 1H), 3.20 (d, J=13.4 Hz, 1H), 3.07-3.02 (m, 1H), 2.19-2.11 (m, 2H), 2.06-1.94 (m, 2H), 1.94-1.83 (m, 2H), 1.75-1.66 (m, 3H), 1.62-1.57 (m, 1H), 1.49-1.34 (m, 1H).

Workup

  1. stirringthe mixture was stirred at rt for about 15 h
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted four times with EtOAc (50 mL)
  4. washThe combined organics were washed twice with brine (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe material was triturated with EtOAc
  9. filtrationthe solids collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-53478a982c614bffb0bc21fda3c7b7d5
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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