Tetrahydrofuran → HCID 86658229, compound

HRID 2169985Notes

Reaction equation

HRID 2169985 reaction equation
OC[CH:3]1[CH2:8][CH2:7][CH:6]([C:9]([NH:11][CH:12]([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[H-].[Na+].[N+:17]([C:20]1[CH:27]=[CH:26][CH:25]=[C:24]([N+]([O-])=O)[C:21]=1[C:22]#[N:23])([O-:19])=[O:18].C1C[O:34][CH2:33]C1>>[C:22]([C:21]1[C:20]([N+:17]([O-:19])=[O:18])=[CH:27][CH:26]=[CH:25][C:24]=1[O:34][CH2:33][C:6]1([C:9]([NH:11][CH:12]([CH3:13])[CH3:14])=[O:10])[CH2:5][CH2:4][CH2:3][CH2:8][CH2:7]1)#[N:23]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 520718DinitrobenzonitrileHCID 66746794HCID 66746794, compound

Product 1

HCID 86658229HCID 86658229, compoundYield 71%

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(hydroxymethyl)-N-isopropylcyclohexanecarboxamide (Example 126d, 480 mg, 2.41 mmol) in dry THF (10 mL) was added NaH (60% in mineral oil, 116 mg, 4.82 mmol) in small portions at 0° C. under N2. The reaction mixture was stirred at 0° C. under N2 for 2 h. To this solution was added 2,6-dinitrobenzonitrile (465 mg, 2.41 mmol), and the reaction mixture was stirred at 0° C.-RT for another 2 h, and then at 60° C. overnight under N2 and cooled down to room temperature. The reaction was quenched with brine, and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (eluent: 50% EtOAc in hexanes) to give the title compound as yellow solid (594 mg, 71%). 1H NR (400 MHz, DMSO-d6) δ 1.00 (d, J=7.6 Hz, 6H), 1.22-2.08 (m, 9H), 2.19 (m, 1H), 3.79 (m, 1H), 4.15 (d, J=7.6 Hz, 2H), 7.45 (brs, 1H), 7.78 (d, J=7.2 Hz, 1H), 7.88 (m, 2H). MS 346 (H+).

Workup

  1. stirringthe reaction mixture was stirred at 0° C.-RT for another 2 h
  2. temperatureat 60° C. overnight under N2 and cooled down to room temperature
  3. customThe reaction was quenched with brine
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by chromatography on silica gel (eluent: 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f1a3920f32644bf4907d8d241b67aa0c
Source dataset
uspto-grants-2015_06
Patent number
US09049878B2

Reaction notes

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