4-(Tert-butoxy)-4-oxobutanoic acid → (R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate

HRID 1945064Notes

Reaction equation

HRID 1945064 reaction equation
[C:1]([O:5][C:6](=[O:12])[CH2:7][CH2:8][C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:14][C@H:15]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=1)[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[Br:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][C@@H:15]([NH:14][C:9](=[O:11])[CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:12])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 41391074-(Tert-butoxy)-4-oxobutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86648197(R)-ethyl 3-amino-4-(4-bromophenyl)butanoate hydrochloride

Product 1

HCID 59607774(R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoateYield 72.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-tert-butoxy-4-oxobutanoic acid (2.38 g, 13.64 mmol) in DMF (30 mL) and DCM (30 mL) is added (R)-ethyl 3-amino-4-(4-bromophenyl)butanoate hydrochloride (4 g, 12.4 mmol), HATU (5.19 g, 13.64 mmol), and TEA (6.91 mL, 49.6 mmol). After stirring at room temperature for 2 hours, the reaction is quenched with H2O, and the crude is diluted with EtOAc, the organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give (R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate (4.0 g). HPLC retention time=1.70 minutes (condition A); MS (m+1)=444.1.

Workup

  1. customthe reaction is quenched with H2O
  2. additionthe crude is diluted with EtOAc
  3. washthe organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-297c8dd74f274e2897748b51be009eab
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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