Pyridine → tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamate

HRID 735530Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 735530
C(Cl)(=O)[C:2](Cl)=[O:3].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH2:18][CH3:19])C(O)=O)=[CH:10][CH:9]=1.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=1)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:18][CH2:19][C:2]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=2)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:3])=[CH:12][CH:13]=1

Komponenten

8

Edukt 4

HCID 1049PyridineHCID 574722-(4-Bromophenyl)butanoic acidHCID 65578Oxalyl chlorideHCID 57956368tert-Butyl 5-amino-2-(ethylthio)benzyl(methyl)carbamate

Produkt 1

HCID 57956370tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamateAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Oxalyl chloride (0.180 mL, 2.06 mmol) was added dropwise to a suspension of 4-bromophenylbutanoic acid (0.250 g, 1.03 mmol) in DCM (3 mL) containing DMF (1 drop) at rt. After 4 h, the reaction mixture was concentrated in vacuo and coevaporated with toluene. The residue was dissolved in DCM (2 mL) and added dropwise to a solution of 17A (0.300 g, 1.01 mmol), DMAP (0.025 g, 0.2 mmol)and pyridine (1.0 mL, 12.3 mmol) in DCM (2 mL) at rt. The reaction mixture was stirred overnight at rt. The reaction mixture was concentrated in vacuo and the residue was triturated with water and then purified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes) to give 17B (0.46 g, 88%) as a clear oil that solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.03 Hz, 3 H) 1.33-1.58 (m, 9 H) 1.96-2.04 (m, 2 H) 2.33 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.74-2.93 (m, 3 H) 4.56 (br. s., 2 H) 6.96-7.02 (m, 0.5 H) 7.05 (d, J=8.35 Hz, 2 H) 7.13 (br. s., 0.4 H) 7.28-7.36 (m, 0.8 H) 7.38 (d, J=8.35 Hz, 2 H) 7.60-7.72 (m, 0.4 H) 7.81-7.98 (m, 0.9 H) 8.33 (br. s., 1 H).

Aufarbeitung

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was triturated with water
  5. custompurified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-299951a814644dfe8887de927b87117a
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07592331B2

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