1-Benzyl-3-bromo-5-chloro-2-pyridone → 4-(1-benzyl-5-chloro-2-oxo-3-pyridinyl)-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl ester

HRID 895893Notes

Reaction equation

HRID 895893 reaction equation
[CH2:1]([N:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[C:10](Br)[C:9]1=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][O:18][C:19](=[O:49])[C@H:20]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Sn](CCCC)(CCCC)CCCC)=[CH:32][CH:31]=1)[NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23]>CN(C=O)C.ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:17][O:18][C:19](=[O:49])[C@H:20]([CH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:10]2[C:9](=[O:16])[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:13]=[C:12]([Cl:14])[CH:11]=2)=[CH:34][CH:35]=1)[NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23]

Participants

6

Reactant 2

HCID 223820541-Benzyl-3-bromo-5-chloro-2-pyridoneHCID 59912887N-Boc-4-(Tributylstannyl)-L-phenylalanine Methyl Ester

Product 1

HCID 697167204-(1-benzyl-5-chloro-2-oxo-3-pyridinyl)-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl esterYield 52.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 1-benzyl-3-bromo-5-chloro-2-pyridone (296 mg, 0.98 mmol) and N-[(1,1-dimethylethoxy)carbonyl]-4-[(tributyl)stannyl]-L-phenylalanine methyl ester (560 mg, 0.99 mmol) in DMF (15 mL) was deoxygenated by alternately freezing the mixture in a liquid nitrogen bath under vacuum and thawing under argon (3×). Bis(triphenylphosphine)palladium dichloride (80 mg, 0.11 mmol) was added and the mixture was heated to 90° C. for 4 hr as the mixture turned dark. An additional 60 mg of the catalyst was added and heating continued for 2 hr. The mixture was allowed to cool, was diluted with dichloromethane, and was filtered through a pad of celite. The filtrate was evaporated to dryness and the residue was chromatographed over 150 g of silica gel eluting with 1:2 ethyl acetate:hexane to give 4-(1-benzyl-5-chloro-2-oxo-3-pyridinyl)-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl ester (255 mg, 52%). LMS-Electrospray: m/z 1015 (2M+Na) (4 Cl) 519 (M+Na) 514 (M+NH4) 497 (M+H).

Workup

  1. temperatureheating
  2. temperatureto cool
  3. filtrationwas filtered through a pad of celite
  4. customThe filtrate was evaporated to dryness
  5. customthe residue was chromatographed over 150 g of silica gel eluting with 1:2 ethyl acetate

Sources & evidence

ORD record
ord-2aa3b9efe079439ab2d4d1a7ad6157fc
Source dataset
uspto-grants-2005_07
Patent number
US06916933B2

Reaction notes

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