Cesium carbonate → HCID 59730164, compound

HRID 228166Notes

Reaction equation

HRID 228166 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]([O:11][C:12](=[O:25])[NH:13][CH2:14][C:15]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)([CH3:17])[CH3:16])([CH3:10])([CH3:9])[CH3:8].Cl[C:27]1[CH:35]=[CH:34][C:30]([C:31]([NH2:33])=[O:32])=[CH:29][N:28]=1>CN(C)C=O.[Cl-].[Na+].O>[C:7]([O:11][C:12](=[O:25])[NH:13][CH2:14][C:15]([C:18]1[CH:19]=[CH:20][C:21]([O:24][C:27]2[CH:35]=[CH:34][C:30]([C:31](=[O:32])[NH2:33])=[CH:29][N:28]=2)=[CH:22][CH:23]=1)([CH3:17])[CH3:16])([CH3:8])([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 804566-ChloronicotinamideHCID 16736951HCID 16736951, compound

Product 1

HCID 59730164HCID 59730164, compoundYield 40.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Add cesium carbonate (2.15 g, 6.60 mmol) to a stirred solution of [2-(4-hydroxy-phenyl)-2-methyl-propyl]-carbamic acid tert-butyl ester (0.86 g, 3.24 mmol) in dimethylformamide (20 mL). Stir for 30 minutes under nitrogen at room temperature. Then add 6-chloronicotinamide (0.51 g, 3.26 mmol) and heat to 100° C. under nitrogen for 6 h. Cool the reaction to room temperature, pour into brine (100 mL), extract with ethyl acetate (3×75 mL), dry the ethyl acetate extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 0.7% concentrated ammonium hydroxide/7% ethanol/chloroform to yield 0.5043 g (40%) of {2-[4-(5-carbamoyl-pyridin-2-yloxy)-phenyl]-2-methyl-propyl}-carbamic acid tert-butyl ester: mass spectrum (ion spray): m/z=386.2 (M+1); 1H NMR (CDCl3): 8.64 (d, 1H), 8.20 (dd, 1H), 7.40 (d, 2H), 7.12 (d, 2H), 6.98 (d, 1H), 4.38 (br s, 1H), 3.34 (d, 2H), 1.75 (br s, 2H), 1.41 (s, 9H), 1.34 (s, 6H).

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. extractionextract with ethyl acetate (3×75 mL)
  4. dry with materialdry the ethyl acetate
  5. filtrationfilter
  6. concentrationconcentrate on a rotary evaporator
  7. customto give the crude product
  8. customThe crude product is purified by flash chromatography on silica gel eluting with 0.7% concentrated ammonium hydroxide/7% ethanol/chloroform

Sources & evidence

ORD record
ord-6983ecf06b2141f39f19f9774bc2aa1c
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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