Iodine → Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(2-methoxypyridin-4-yl)propanoate

HRID 58797Notes

Reaction equation

HRID 58797 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14]I)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].II.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.Br[C:48]1[CH:53]=[CH:52][N:51]=[C:50]([O:54][CH3:55])[CH:49]=1>[Zn].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].O.CCOC(C)=O.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:48]1[CH:53]=[CH:52][N:51]=[C:50]([O:54][CH3:55])[CH:49]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 4

HCID 807IodineHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 140623094-Bromo-2-methoxypyridine

Product 1

HCID 86681449Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(2-methoxypyridin-4-yl)propanoateYield 73%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dry DMF (30 mL) was added to zinc dust (2.78 g, 42.6 mmol) in a flame dried bottom flask under N2. (R)-Methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (3.85 g, 11.7 mmol) was added followed by a catalytic amount of iodine (1.06 g, 0.10 mmol). The mixture was stirred at ambient temperature for 0.5 h. Pd2(dba)3 (487 mg, 0.050 mmol), S—Phos (437 g, 0.100 mmol) and 4-bromo-2-methoxypyridine (2.00 g, 10.6 mmol) were added. The reaction mixture was heated at 60° C. for 6 h and then cooled to ambient temperature. EtOAc (200 mL) and water (200 mL) were added. The organic phase was separated, washed with water (300 mL×3) and brine (300 mL×1), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (hexane/EtOAc=2:1) to afford (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2-methoxypyridin-4-yl)propanoate (2.4 g, 73% yield).

Workup

  1. customdried bottom flask under N2
  2. temperatureThe reaction mixture was heated at 60° C. for 6 h
  3. temperaturecooled to ambient temperature
  4. customThe organic phase was separated
  5. washwashed with water (300 mL×3) and brine (300 mL×1)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel (hexane/EtOAc=2:1)

Sources & evidence

ORD record
ord-ab0ee715958343f1bbacd511500094fe
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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