Sulfuric Acid → HCID 53253753, compound

HRID 1464885Notes

Reaction equation

HRID 1464885 reaction equation
Br[C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[N:4]([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Li]CCCC.[C:21]1(=O)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.OS(O)(=O)=O>C1COCC1>[CH3:11][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:21]2([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:2]2[CH:15]=[CH:14][CH:13]=[CH:12][C:3]1=2

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 7967CyclohexanoneHCID 53253553HCID 53253553, compoundHCID 178418339Butyllithium

Product 1

HCID 53253753HCID 53253753, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A flame-dried two-necked flask was charged with 2-bromo-N-methyl-N-phenylaniline (1.0 g, 3.8 mmol) and 100 mL dry THF under argon and cooled to −78° C. in a dry ice-acetone bath. 2.6 mL of a 1.6 M solution of n-BuLi in hexanes (4.16 mmol) was added dropwise over 5 minutes and the reaction stirred at −78° C. under argon for 1 h. Cyclohexanone (0.43 mL, 0.412 g, 4.2 mmol) was added in one portion to the reaction mixture at −78° C., the reaction allowed to warm to room temperature and stirred overnight under argon. After quenching with saturated ammonium chloride, the reaction was extracted with Et2O, the organic layers combined, washed with brine and water and dried over anhydrous MgSO4 and the solvent evaporated under reduced pressure. To the neat residue thus obtained was added 2 mL of concentrated H2SO4 under argon and the mixture stirred at room temperature for 1 h under argon. After dilution with 30 mL DI H2O, the reaction was extracted with Et2O (5×50 mL), the organic layers were combined, washed with brine and water and dried over anhydrous MgSO4, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography using hexanes as the eluent to yield 0.3 g (30%) of the desired compound as a clear oil. 1H NMR (400 MHz, CHCl3) δ 1.53 (m, 4H), 2.10 (m, 4H), 3.12 (s, 3H), 5.65 (m, 1H), 6.66 (m, 3H), 7.18 (m, 6H). 13C NMR (100 MHz, CHCl3) δ 22.0, 23.0, 25.6, 28.2, 39.2, 113.7, 116.9, 125.6, 126.3, 127.7, 128.2, 128.5, 130.3, 137.9, 142.8, 145.6, 149.0. HRMS (ESI) calc for C19H21N [M+H]+ 264.1747, found 264.1758. IR (KBr plate) 693 (m), 747(m), 1069 (s), 1155 (m), 1263 (m), 1345 (m), 1499 (s), 1602(s), 2853 (m), 2921 (s) cm−1.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight under argon
  3. customAfter quenching with saturated ammonium chloride
  4. extractionthe reaction was extracted with Et2O
  5. washwashed with brine and water
  6. dry with materialdried over anhydrous MgSO4
  7. customthe solvent evaporated under reduced pressure
  8. customTo the neat residue thus obtained
  9. stirringthe mixture stirred at room temperature for 1 h under argon
  10. extractionAfter dilution with 30 mL DI H2O, the reaction was extracted with Et2O (5×50 mL)
  11. washwashed with brine and water
  12. dry with materialdried over anhydrous MgSO4
  13. customthe solvent was evaporated under reduced pressure
  14. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b83b94b39db749f1a812c20449ad1a65
Source dataset
uspto-grants-2015_04
Patent number
US08999722B2

Reaction notes

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