Nitrogen → (2S,3R)-Methyl 2-(4-((4-formylphenyl)ethynyl)benzamido)-3-hydroxybutanoate

HRID 1692518Notes

Reaction equation

HRID 1692518 reaction equation
[OH:1][C@H:2]([CH3:25])[C@H:3]([NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14](C(C2C=CC=CC=2)=O)=[CH:13][CH:12]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].C(OC(NCC(N[C:38]1[CH:43]=[CH:42]C(I)=[CH:40][CH:39]=1)=O)=O)(C)(C)C.CCN(CC)CC.N#N.[CH2:54]1[CH2:58][O:57][CH2:56][CH2:55]1>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.[Cu]I>[CH3:7][O:6][C:4](=[O:5])[C@@H:3]([NH:8][C:9](=[O:10])[C:11]1[CH:16]=[CH:15][C:14]([C:42]#[C:43][C:38]2[CH:56]=[CH:55][C:54]([CH:58]=[O:57])=[CH:40][CH:39]=2)=[CH:13][CH:12]=1)[C@H:2]([OH:1])[CH3:25]

Participants

8

Reactant 5

HCID 947NitrogenHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 474512392-[(tert-butoxy)carbonylamino]-N-(4-iodophenyl)acetamideHCID 59697585methyl(2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate

Product 1

HCID 59697530(2S,3R)-Methyl 2-(4-((4-formylphenyl)ethynyl)benzamido)-3-hydroxybutanoateYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

A solution of alkyne 1 (745 mg, 2.85 mmol), 4-iodobenzaldehyde 2 (902 mg, 3.89 mmol), and Et3N (900 μL, 6.5 mmol) in THF (50 mL) was purged with a stream of N2 for two minutes and then treated with PdCl2(PPh3)2 (70 mg, 0.10 mmol) and CuI (34 mg, 0.18 mmol). The reaction mixture was stirred 40 h, concentrated by rotary evaporation and purified by silica gel chromatography (40:1 DCM/MeOH) to give 0.833 g (80% yield) of (2S,3R)-2-[4-(4-formyl-phenylethynyl)-benzoylamino]-3-hydroxy-butyric acid methyl ester 3 as a pale yellow powder, mp=143-144° C. Rf=0.3 (25:1 DCM/MeOH); LRMS (ES+) m/z 366.1 (C21H19NO5+H requires 366.13); HPLC (300 nm, 47 min) 15.3 min.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. custompurified by silica gel chromatography (40:1 DCM/MeOH)

Sources & evidence

ORD record
ord-fcbae179af35405ea597f969f4158c40
Source dataset
uspto-grants-2012_04
Patent number
US08153843B2

Reaction notes

Loading…