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

HRID 869795

Reaction equation

HRID 869795 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 for 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-92b28bb3c68e439a87e4d6ed2859d151
Source dataset
uspto-grants-2015_03
Patent number
US08969354B2

Linked notes

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