Triethylamine → 2-(4-(Tert-butoxycarbonyl)-1-(4,5-dichloro-2-nitrophenyl)piperazin-2-yl)acetic acid

HRID 1035277

Reaction equation

HRID 1035277 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5](F)=[CH:4][C:3]=1[Cl:12].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH:22]([CH2:26][C:27]([OH:29])=[O:28])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>CN(C)C=O.O>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:5]2[CH:4]=[C:3]([Cl:12])[C:2]([Cl:1])=[CH:7][C:6]=2[N+:8]([O-:10])=[O:9])[CH:22]([CH2:26][C:27]([OH:29])=[O:28])[CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 5339511,2-Dichloro-4-fluoro-5-nitrobenzeneHCID 446077242-(4-(tert-Butoxycarbonyl)piperazin-2-yl)acetic acid

Product 1

HCID 672493902-(4-(Tert-butoxycarbonyl)-1-(4,5-dichloro-2-nitrophenyl)piperazin-2-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1,2-Dichloro-4-fluoro-5-nitrobenzene (0.125 mL, 0.952 mmol) and 2-(4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid (256 mg, 1.048 mmol) were dissolved in N,N-dimethylformamide (2 mL) and water (1 mL). Triethylamine (0.398 mL, 2.86 mmol) was slowly added. The resulting mixture was heated at 50° C. overnight. The mixture was concentrated and ethyl acetate was added. 1 N HCl was then added slowly until the pH=6. The water layer was separated and washed multiple times with ethyl acetate. The organic layers were then combined and concentrated. The crude material was purified by silica gel chromatography eluting with a gradient of 10% to 50% of ethyl acetate in hexane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.32 (br, 1H), 8.17 (s, 1H), 7.69 (s, 1H), 3.36-3.90 (m, 4H), 2.97-3.29 (m, 2H), 2.88 (dd, J=8.92, 3.37 Hz, 1H), 2.18-2.47 (m, 2H), 1.41 (s, 9H); MS (DCI+) m/z 434.1 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. additionethyl acetate was added
  3. addition1 N HCl was then added slowly until the pH=6
  4. customThe water layer was separated
  5. washwashed multiple times with ethyl acetate
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a gradient of 10% to 50% of ethyl acetate in hexane

Sources & evidence

ORD record
ord-8f16ccf92fca4fb8ace579f73593c7be
Source dataset
uspto-grants-2013_10
Patent number
US08546377B2

Linked notes

Loading…