4-Nitrobenzoic Acid → HCID 178525742, compound

HRID 2235270Notes

Reaction equation

HRID 2235270 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([OH:16])[CH2:12][CH2:11]2)[C:6]1=[O:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[N+:54]([C:57]1[CH:65]=[CH:64][C:60]([C:61](O)=[O:62])=[CH:59][CH:58]=1)([O-:56])=[O:55]>C1COCC1>[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([C@@H:10]2[CH2:11][CH2:12][C@H:13]([O:16][C:61](=[O:62])[C:60]3[CH:59]=[CH:58][C:57]([N+:54]([O-:56])=[O:55])=[CH:65][CH:64]=3)[CH2:14][CH2:15]2)[C:6]1=[O:17]

Participants

6

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178515596HCID 178515596, compound

Product 1

HCID 178525742HCID 178525742, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

Dissolve 3-(2,4-dichloro-benzyl)-1-(trans-4-hydroxy-cyclohexyl)-pyrrolidin-2-one (Example 15) (3.32 g, 9.70 mmol) in anhydrous THF (200 mL) and cool to −20 ° C. Add triphenyl phosphine (12.71 g, 48.48 mmol), diethyl azodicarboxylate (8.44 g, 48.48 mmol), and 4-nitro-benzoic acid (8.10 g, 48.48 mmol). Stir the reaction mixture for 6 hours at the same temperature, then warm the reaction to room temperature and continue to stir the reaction overnight. Add water (200 mL) and extract the aqueous layer with ethyl acetate (3×200 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 30-60% of EtOAc-Hexane) to give 1.76 g (100%) of the title compound as a white solid: 1H NMR (CDCl3) δ 8.28-8.32 (m, 2H), 8.17-8.24 (m, 2H), 7.38 (d, 1H), 7.23 (d, 1H), 7.18 (dd, 1H), 5.28-5.32 (m, 1H), 4.05-4.15 (m, 1H), 3.25-3.40 (m, 3H), 2.74-2.83 (m, 2H), 2.10-2.23 (m, 1H), 2.02-2.10 (m, 1H), 1.60-1.92 (m, 8H).

Workup

  1. temperaturewarm
  2. customthe reaction to room temperature
  3. stirringto stir
  4. customthe reaction overnight
  5. extractionAdd water (200 mL) and extract the aqueous layer with ethyl acetate (3×200 mL)
  6. dry with materialCombine the organic layers and dry with Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by flash column chromatography (silica gel, 30-60% of EtOAc-Hexane)

Sources & evidence

ORD record
ord-197eece84ebf456c8a946cc4faf18c5e
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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