Nitrogen → Tert-butyl {1-[5-chloro-3-(6-formylpyridin-3-yl)-2-methoxy-4-methylphenyl]ethyl}carbamate

HRID 510987Notes

Reaction equation

HRID 510987 reaction equation
Br[C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[CH:32][C:33]([CH:36]=[O:37])=[N:34][CH:35]=2)O1.C(=O)([O-])[O-].[K+].[K+].N#N>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:30]2[CH:35]=[N:34][C:33]([CH:36]=[O:37])=[CH:32][CH:31]=2)[C:3]([O:20][CH3:21])=[C:4]([CH:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 447548395-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbaldehydeHCID 88543336Tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate

Product 1

HCID 86666904Tert-butyl {1-[5-chloro-3-(6-formylpyridin-3-yl)-2-methoxy-4-methylphenyl]ethyl}carbamateYield 74.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of tert-butyl [1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate (200 mg, 0.5 mmol, from Example 113, Step 1 peak 2) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbaldehyde (150 mg, 0.63 mmol, Frontier Scientific, catalog# F2110) in 1,4-dioxane (4 mL) was added potassium carbonate (200 mg, 2 mmol) in water (2 mL). The reaction was degassed with N2 and tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.04 mmol) was added and degassed again with N2. The reaction was heated at 100° C. overnight. The reaction was allowed to cool to room temperature and was partitioned between water and EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by chromatography on silica gel eluting with a hexane:EtOAc gradient to give tert-butyl {1-[5-chloro-3-(6-formylpyridin-3-yl)-2-methoxy-4-methylphenyl]ethyl}carbamate as a yellow oil (0.15 g, 70%). LCMS calculated for C21H26ClN2O4(M+H)+: m/z=405.2. found: 405.1.

Workup

  1. additionwas added
  2. customdegassed again with N2
  3. temperatureto cool to room temperature
  4. customwas partitioned between water and EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThe product was purified by chromatography on silica gel eluting with a hexane

Sources & evidence

ORD record
ord-0aa13cbd7a68450ea9a6e970db09bd47
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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