Diisopropylethylamine → (S,E)-tert-butyl 6-(4-methoxy-4-oxobut-2-enamido)-2-((2-(trimethylsilyl)ethoxy)carbonyl)hexanoate

HRID 926915Notes

Reaction equation

HRID 926915 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@@H:6]([C:14]([O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[O:15])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[C:23]([O:30][CH3:31])(=[O:29])/[CH:24]=[CH:25]/[C:26]([O-])=[O:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[CH3:31][O:30][C:23](=[O:29])/[CH:24]=[CH:25]/[C:26]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C@@H:6]([C:14]([O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[O:15])[C:7]([O:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[O:8])=[O:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21721168(E)-4-methoxy-4-oxobut-2-enoateHCID 86655432(S)-tert-butyl 6-amino-2-((2-(trimethylsilyl)ethoxy)carbonyl)hexanoate

Product 1

HCID 86655431(S,E)-tert-butyl 6-(4-methoxy-4-oxobut-2-enamido)-2-((2-(trimethylsilyl)ethoxy)carbonyl)hexanoateYield 87.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirring mixture of (S)-tert-butyl 6-amino-2-((2-(trimethylsilyl)ethoxy)carbonyl)hexanoate (800 mg, 2.31 mmol), monomethyl fumarate (361 mg, 2.77 mmol), DIEA (1.1 mL, 6.93 mmol) in 10 mL acetonitrile was added HATU (1.14 g, 3.00 mmol) in one portion at 0° C. under an inert atmosphere of argon. The resulting reaction mixture was stirred at room temperature tor 2 h and then concentrated under reduced pressure. The resulting residue was diluted with EtOAc (50 mL) and washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc/pentane) afforded (S,E)-tert-butyl 6-(4-methoxy-4-oxobut-2-enamido)-2-((2-(trimethylsilyl)ethoxy)carbonyl)hexanoate (900 mg, 85%).

Workup

  1. customThe resulting reaction mixture
  2. concentrationconcentrated under reduced pressure
  3. additionThe resulting residue was diluted with EtOAc (50 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography (EtOAc/pentane)

Sources & evidence

ORD record
ord-cd0762a8e08e4d948b65eecd9e505251
Source dataset
uspto-grants-2016_03
Patent number
US09289503B2

Reaction notes

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