2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 131732969, compound

HRID 2173374Notes

Reaction equation

HRID 2173374 reaction equation
Br[C:2]1[C:3]([CH2:15][CH2:16][OH:17])=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[Cl-].[C:53]([O:57][C:58](=[O:61])[CH2:59][Zn+])([CH3:56])([CH3:55])[CH3:54]>C(OCC)C.C(OCC)(=O)C.[OH-].[NH4+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:53]([O:57][C:58](=[O:61])[CH2:59][C:2]1[CH:7]=[N:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[CH2:15][CH2:16][OH:17])([CH3:56])([CH3:55])[CH3:54]

Participants

8

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 67516965HCID 67516965, compoundHCID 178451183HCID 178451183, compound

Product 1

HCID 131732969HCID 131732969, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
45 °C

Procedure

A 250 mL round bottomed flask was charged with N-[5-bromo-4-(2-hydroxyethyl)pyridin-2-yl]-2,2-dimethylpropanamide (1.9 g, 6.31 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.173 g, 0.189 mmol), and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.180 g, 0.379) and the mixture was flushed with nitrogen for 30 min. tetrahydrofuran was added, followed by a solution of 2-tert-butoxy-2-oxoethylzinc chloride in diethyl ether (0.5 M, 47.9 mL) and the mixture was placed in an oil bath maintained at 45° C. After 12 h, the reaction was recharged with tris(dibenzylideneacetone)dipalladium(0) (0.173 g, 0.189 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.180 g, 0.379) and an additional quandity of 2-tert-butoxy-2-oxoethylzinc chloride in diethyl ether (0.5 M, 12.6 mL) was added. After stirring an additional 2 h in the 45° C. bath, the reaction mixture was diluted with ethyl acetate and 10% ammonium hydroxide solution, filtered to remove solids, and the layers separated. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated. Purification by MPLC (eluent 9-90% ethyl acetate/hexanes) afforded tert-butyl{6-[(2,2-dimethylpropanoyl)amino]-4-(2-hydroxyethyl)pyridin-3-yl}acetate. 1H NMR (500 MHz, CDCl3), δ 8.30 (br s, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 3.88 (dd, J=6.5, 6.5 Hz, 2H), 3.55 (s, 2H), 2.88 (dd, J=6.5, 6.5 Hz, 2H), 1.40 (s, 9H), 1.28 (s, 9H); LC/MS (M+1)+=337.0;

Workup

  1. customthe mixture was flushed with nitrogen for 30 min. tetrahydrofuran
  2. additionwas added
  3. customthe mixture was placed in an oil bath
  4. filtrationfiltered
  5. customto remove solids
  6. customthe layers separated
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by MPLC (eluent 9-90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-57df93dcc420428abdd283939c8bf2bf
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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