Diisopropylethylamine → (S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 18354

Reaktionsgleichung

Reaktionsgleichung von HRID 18354
Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=1)=[O:5].[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[C:25](O)=[O:26])=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(C(C)C)CC)(C)C.C(OP(ON1C(=O)C2C=CC=CC=2N=N1)(OCC)=O)C>CN(C=O)C.O.C(OCC)(=O)C>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([C:4](=[O:5])[CH2:3][NH:2][C:25]([C@@H:21]2[CH2:22][CH2:23][CH2:24][N:20]2[C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])=[O:26])=[CH:7][CH:8]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one

Produkt 1

HCID 56605334(S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylateAusbeute 56,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Versuchsvorschrift

To a solution of 2-amino-1-(4-bromophenyl)ethanone hydrochloride salt (1.10 g, 4.39 mmol), (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (1.02 g, 4.73 mmol), and diisopropylethylamine (3.10 mL, 17.4 mmol) in DMF (20 mL) was added 3-(diethoxyphosphoryloxy)-(1,2,3)-benzotriazin-4(3H)-one (DEPBT, 2.0 g, 6.68 mmol) and the solution was allowed to stir for 2 hours. The mixture was poured into H2O-ethyl acetate and the layers were separated. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed (H2O×2, brine), dried (Na2SO4), and filtered. The solvent was removed in vacuo and the residue purified by flash column chromatography (1:1 hexanes:ethyl acetate) to provide (S)-tert-butyl 2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)pyrrolidine-1-carboxylate (1.02 g, 56%) as a colorless foam. 1HNMR (400 MHz, DMSO-d6) δ 8.16-8.21 (m, 1H), 7.90-7.92 (m, 2H), 7.73-7.75 (m, 2H), 4.59 (dd, J=5.7, 18.4 Hz, 1H), 4.51 (dd, J=5.7, 18.4 Hz, 1H), 4.13-4.19 (m, 1H), 3.24-3.27 (m, 2H, partially obscured by H2O), 2.05-2.12 (m, 1H), 1.74-1.81 (m, 3H), 1.39 (s, 3H), 1.33 (3, 6H); LCMS: Anal. Calcd. for C18H23BrN2O4: 410. found: 411 (M+H)+.

Aufarbeitung

  1. customthe layers were separated
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. washthe combined organic layers were washed (H2O×2, brine)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by flash column chromatography (1:1 hexanes:ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-6b1ac0b948bd442b98fce6052c6ab1df
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741347B2

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