Potassium Sodium Tartrate → HCID 72670105, compound

HRID 529393Notes

Reaction equation

HRID 529393 reaction equation
[NH2:1][C:2]1([CH2:18][O:19][CH2:20][CH2:21][C:22]#[N:23])[C:15]2[CH:14]=[C:13]([Cl:16])[N:12]=[CH:11][C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:17])=[CH:6][CH:7]=2.C[Al](C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.O>[Br:17][C:5]1[CH:4]=[C:3]2[C:2]3([N:1]=[C:22]([NH2:23])[CH2:21][CH2:20][O:19][CH2:18]3)[C:15]3[CH:14]=[C:13]([Cl:16])[N:12]=[CH:11][C:10]=3[O:9][C:8]2=[CH:7][CH:6]=1

Participants

7

Reactant 3

HCID 9357Potassium Sodium TartrateHCID 16682925TrimethylaluminumHCID 86709314HCID 86709314, compound

Product 1

HCID 72670105HCID 72670105, compoundYield 15.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 500-mL RBF was charged with 3-((5-amino-7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-yl)methoxy)propanenitrile (3.967 g, 10.05 mmol) and toluene (100 mL) to give a clear solution. Trimethylaluminum (10.55 mL of a 2M solution in toluene, 21.11 mmol) was added, and the resulting mixture was stirred for 5 min. A reflux condenser was attached, and the mixture was heated to reflux for 1 h. After the mixture had cooled to RT, a saturated aq. Rochelle's salt solution (200 mL) was slowly added. The mixture was stirred vigorously for 48 h and was then diluted with EtOAc (200 mL) and water (300 mL). The layers were separated, and the aq. layer was extracted with EtOAc (2×200 mL). The combined organic extracts were washed with water (200 mL), washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was taken up in DCM/MeOH and filtered to give 615 mg of the desired product an off-white solid. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (0-10% MeOH/DCM). The product obtained from chromatography was combined with the above solid to give 7-bromo-3-chloro-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazepin]-5′-amine as a cream-colored solid. 1H NMR (400 MHz, DMSO-d6) δ=8.37 (d, J=0.4 Hz, 1 H), 7.62-7.43 (m, 2 H), 7.35 (s, 1 H), 7.22 (dd, J=0.5, 8.4 Hz, 1 H), 6.27 (br. s., 2 H), 3.94-3.72 (m, 2H), 3.70-3.47 (m, 2 H), 3.05-2.75 (m, 2 H). MS m/z=394.0. Calc'd for C16H14BrClN3O2: 394.0.

Workup

  1. customto give a clear solution
  2. customA reflux condenser was attached
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 1 h
  5. stirringThe mixture was stirred vigorously for 48 h
  6. customThe layers were separated
  7. extractionthe aq. layer was extracted with EtOAc (2×200 mL)
  8. washThe combined organic extracts were washed with water (200 mL)
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. filtrationfiltered

Sources & evidence

ORD record
ord-f39233af577a49ceb7ccf46ffcdd4bcf
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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