Dimethylformamide → 1-(9H-fluoren-9-yl)methyl 4-tert-butyl 2-(2-(2-bromophenylamino)-2-oxoethyl)piperazine-1,4-dicarboxylate

HRID 1896103

Reaction equation

HRID 1896103 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH:9]1[C:21]2[CH:20]([CH2:22][O:23][C:24]([N:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]3[CH2:39][C:40](O)=[O:41])=[O:25])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.CN(C)C=O.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[Br:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:40](=[O:41])[CH2:39][CH:27]1[CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31][N:26]1[C:24]([O:23][CH2:22][CH:20]1[C:21]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=2[C:14]2[C:19]1=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:25]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 119922-BromoanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27567961-Fmoc-4-Boc-Piperazine-2-acetic acid

Product 1

HCID 582849301-(9H-fluoren-9-yl)methyl 4-tert-butyl 2-(2-(2-bromophenylamino)-2-oxoethyl)piperazine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 2-bromoaniline (3.69 g, 21.44 mmol), and 2-(1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid (10 g, 21.44 mmol) in a 1:1 solution of N,N-dimethylformamide:pyridine (100 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (10.27 g, 53.6 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and was subsequently washed with brine (3×) and 1 M HCl (3×). The organic solution was then concentrated onto silica gel and purified via flash chromatography (10-70% ethyl acetate/hexanes) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.43 (s, 1 H), 7.81-7.95 (m, J=7.67 Hz, 2 H), 7.53-7.75 (m, 4 H), 7.22-7.48 (m, 5 H), 7.10 (dd, J=7.21 Hz, 1 H), 4.56 (s, 1 H), 4.17-4.42 (m, 3 H), 3.61-3.98 (m, 3 H), 2.89-3.18 (m, 2 H), 2.62-2.88 (m, 2 H), 2.49-2.58 (m, 1 H), 1.32-1.50 (m, 9 H); MS (APCI+) m/z 522.2 (M-Boc+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. washwas subsequently washed with brine (3×) and 1 M HCl (3×)
  4. concentrationThe organic solution was then concentrated onto silica gel
  5. custompurified via flash chromatography (10-70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4be111d48f754ccd8f62489f94b6f4f7
Source dataset
uspto-grants-2013_08
Patent number
US08518933B2

Linked notes

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