Cesium carbonate → HCID 86722344, compound

HRID 718765Notes

Reaction equation

HRID 718765 reaction equation
Br[C:2]1[C:3]([NH2:23])=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][CH:8]3[CH2:12][C:13]4([CH2:18][CH2:19][C:7]3([CH2:20][CH3:21])[C:6]=2[CH:22]=1)[O:17][CH2:16][CH2:15][O:14]4.[C:24](=O)([O-])[O-].[Cs+].[Cs+].CB1OB(C)OB(C)O1>COCCOC.O.CCOC(C)=O.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>[CH2:20]([C:7]12[CH2:19][CH2:18][C:13]3([O:14][CH2:15][CH2:16][O:17]3)[CH2:12][CH:8]1[CH2:9][CH2:10][CH2:11][C:5]1[CH:4]=[C:3]([NH2:23])[C:2]([CH3:24])=[CH:22][C:6]=12)[CH3:21]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 574072TrimethylboroxineHCID 86722343HCID 86722343, compound

Product 1

HCID 86722344HCID 86722344, compoundYield 53%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of rac-(4aR,11bS)-10-bromo-11b-ethyl-1,2,4,4a,5,6,7,11b-octahydrospiro[dibenzo[a,c][7]annulene-3,2′-[1,3]dioxolan]-9-amine (23, R2=Ethyl) (0.255 g, 0.670 mmol) in DME (6 mL) and water (2 mL) was degassed by bubbling nitrogen through the mixture for about 15 min. Cesium carbonate (0.655 g, 2.011 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (0.168 g, 1.341 mmol) and PdCl2(PPh3)2 (0.024 g, 0.034 mmol) were added and the mixture was heated to about 90° C. for about 22 h. The mixture was cooled to rt, diluted with EtOAc (25 mL) and washed with sat. aq. NaHCO3 (10 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-15% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-(4aR,11bS)-11b-ethyl-10-methyl-1,2,4,4a,5,6,7,11b-octahydrospiro[dibenzo[a,c][7]annulene-3,2′-[1,3]dioxolan]-9-amine (24, R2=Ethyl) (0.112 g, 53%); LC/MS, method 3, Rt=2.53 min, MS m/z 316 (M+H)+. 1H NMR (400 MHz, DMSO) δ 6.72 (s, 1H), 6.35 (s, 1H), 4.61 (s, 2H), 3.88-3.70 (m, 4H), 2.79-2.72 (m, 1H), 2.54-2.47 (m, 1H), 2.33-2.27 (m, 1H), 2.13-2.04 (m, 1H), 2.00 (s, 3H), 1.97-1.88 (m, 2H), 1.72-1.57 (m, 3H), 1.53-1.46 (m, 1H), 1.41-1.14 (m, 5H), 0.59 (t, J=7.4 Hz, 3H).

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through the mixture for about 15 min
  3. temperatureThe mixture was cooled to rt
  4. washwashed with sat. aq. NaHCO3 (10 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel (4 g)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a2377dbbdad84e8f8879b05696345edf
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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