Cesium carbonate → tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 2369514Notes

Reaction equation

HRID 2369514 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1.[C:16]([O:20][C:21](=[O:30])[NH:22][C@@H:23]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:24][OH:25])([CH3:19])([CH3:18])[CH3:17].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:16]([O:20][C:21](=[O:30])[NH:22][CH:23]([CH2:26][CH:27]([CH3:28])[CH3:29])[CH2:24][O:25][C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 866958928-chloro-5H-chromeno[3,4-c]pyridine

Product 1

HCID 86724429tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamateYield 45%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To 8-chloro-5H-chromeno[3,4-c]pyridine (0.489 g, 2.247 mmol) (prepared as in Example 5, Part D), (S)-tert-butyl(1-hydroxy-4-methylpentan-2-yl)carbamate (1.474 g, 6.79 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (0.572 g, 1.348 mmol), palladium (II) acetate (0.151 g, 0.674 mmol) and cesium carbonate (1.098 g, 3.37 mmol) was added toluene (4 mL). Nitrogen gas was bubbled through the mixture for 5 min and the mixture heated at 80° C. for 15 h. The reaction mixture was cooled to room temperature and filtered through a bed of celite. Water (10 mL) was added to the filtrate and the product was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine (1×10 mL), dried with sodium sulfate and concentrated under reduced pressure. The residue so obtained was purified by preparative TLC using (50% ethyl acetate in pet ether) to afford tert-butyl(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.4 g, 1.00 mmol, 45% yield) as a semi solid. LCMS (ESI) m/e 399.2 [(M+H)+, calcd for C23H31N2O4 399.5]; LC/MS retention time (Method C): tR=2.16 min.

Workup

  1. customNitrogen gas was bubbled through the mixture for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through a bed of celite
  4. additionWater (10 mL) was added to the filtrate
  5. extractionthe product was extracted with ethyl acetate (3×15 mL)
  6. washThe combined organic extracts were washed with brine (1×10 mL)
  7. dry with materialdried with sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue so obtained
  10. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-e8afde31dc5d4b12a5b66b39799fcab9
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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