O-Xylene → 4-Cyclopropyl-3-nitropyridine

HRID 523524Notes

Reaction equation

HRID 523524 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH:11]1(B(O)O)[CH2:13][CH2:12]1.C1(C)C(C)=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OC(=O)C)C>[CH:11]1([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 7237O-XyleneHCID 11430Potassium CarbonateHCID 27357814-Chloro-3-nitropyridineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 668018544-Cyclopropyl-3-nitropyridineYield 736.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

4-Chloro-3-nitropyridine (100 mg, 0.630 mmol) and cyclopropyl boronic acid (10.0 mg, 0.091 mmol) were added to a solution of xylene (3 mL) previously purged with argon (10 minutes). The reaction mixture was purged with argon for a further 15 minutes, followed by the addition of potassium carbonate (174.35 mg, 1.26 mmol) and Pd(PPh3)4 (34.5 mg, 0.063 mmol). The resulting mixture was heated to reflux at 130° C. overnight. The reaction was monitored by TLC (30% ethylacetate in hexane). The reaction mixture was cooled and concentrated to afford the crude product. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 110 mg of the product (100% yield). LCMS Purity: 99%, m/z=165 (M+1)

Workup

  1. custompreviously purged with argon (10 minutes)
  2. customThe reaction mixture was purged with argon for a further 15 minutes
  3. temperatureThe resulting mixture was heated
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated
  6. customto afford the crude product
  7. customPurification by column chromatography on silica gel (15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6175eb6066984c32900bc97d4e289272
Source dataset
uspto-grants-2016_05
Patent number
US09339501B2

Reaction notes

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