Pyridine → N-(4-tert-Butyl-2-nitrophenyl)-3-(3-oxocyclobutyl)propanamide

HRID 707672

Reaction equation

HRID 707672 reaction equation
[O:1]=[C:2]1[CH2:5][CH:4]([CH2:6][CH2:7][C:8]([OH:10])=O)[CH2:3]1.[C:11]([C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[C:17]([N+:22]([O-:24])=[O:23])[CH:16]=1)([CH3:14])([CH3:13])[CH3:12].N1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>O1CCOCC1.CCOC(C)=O>[C:11]([C:15]1[CH:21]=[CH:20][C:18]([NH:19][C:8](=[O:10])[CH2:7][CH2:6][CH:4]2[CH2:3][C:2](=[O:1])[CH2:5]2)=[C:17]([N+:22]([O-:24])=[O:23])[CH:16]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 1049PyridineHCID 805734-tert-Butyl-2-nitroanilineHCID 111923Propylphosphonic anhydrideHCID 677753573-(3-Oxocyclobutyl)propanoic acid

Product 1

HCID 90455940N-(4-tert-Butyl-2-nitrophenyl)-3-(3-oxocyclobutyl)propanamideYield 85%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-(3-Oxocyclobutyl)propanoic acid (10) (1.610 g, 11.3 mmol) and 4-tert-butyl-2-nitroaniline (11) (2.000 g, 10.3 mmol) were dissolved in 1,4-dioxane (20 ml) and pyridine (2.6 ml, 30.9 mmol) and T3P (50% solution in EtOAc) (9.1 ml, 15.5 mmol) was added at r.t. The reaction was heated to 100° C. and left for 7 hrs. The reaction was cooled to r.t., diluted with EtOAc (20 ml) and washed with 2M NaOH (2×20 ml), 2M HCl (20 ml), brine (20 ml), dried over MgSO4 and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% heptanes to 40% EtOAc:60% heptanes as eluent to give 12 as a yellow oil (2.776 g, 85%): MS (ESI+) for C17H22N2O4 m/z 319.25 [M+H]+, 341.00 [M+Na]+; LC purity 99% (UV) (ret. time, 2.11 min); 1H NMR (500 MHz, CDCl3) δ 10.28 (s, 1H), 8.66 (d, J=8.9 Hz, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.70 (dd, J=8.9, 2.3 Hz, 1H), 3.30-3.12 (m, 2H), 2.86-2.69 (m, 2H), 2.50 (ddd, J=30.3, 14.9, 7.6 Hz, 3H), 2.07 (q, J=7.6 Hz, 2H), 1.34 (s, 9H).

Workup

  1. temperatureThe reaction was cooled to r.t.
  2. washwashed with 2M NaOH (2×20 ml), 2M HCl (20 ml), brine (20 ml)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThe product was purified by silica flash column chromatography

Sources & evidence

ORD record
ord-84a686e324fb421abda2e2d00a8018ca
Source dataset
uspto-grants-2015_11
Patent number
US09175032B2

Linked notes

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