Potassium Hydroxide → HCID 10074074, compound

HRID 747112Notes

Reaction equation

HRID 747112 reaction equation
[CH2:1]([N:3]([CH2:34][CH3:35])[C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)[C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[C:16]#[N:17])=[CH:8][CH:7]=1)=[O:5])[CH3:2].[OH-:36].[K+]>C(O)(C)(C)C.ClCCl>[CH2:34]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[CH:7]=[CH:8][C:9]([CH:12]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:25][CH2:26]2)[C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[C:16]([NH2:17])=[O:36])=[CH:10][CH:11]=1)=[O:5])[CH3:35]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 11511057HCID 11511057, compound

Product 1

HCID 10074074HCID 10074074, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of INTERMEDIATE 4a (428 mg) in tert-butanol (10 mL) was added crushed potassium hydroxide (129 mg, 2.5 eq) and the reaction was heated to reflux. After 90 minutes the reaction was cooled and diluted with dichloromethane (40 mL). The reaction was washed with water (30 mL) and the organic layer separated. The aqueous layer was neutralized with 2 N hydrochloric acid and washed with dichloromethane (2×25 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography, eluting 3% methanol in dichloromethane to yield COMPOUND 1 as a colorless foam (374.5 mg, 84%). 1H NMR (CD3OD) δ 1.06 (t, J=6.9 Hz, 3H), 1.20 (t, J=6.8 Hz, 3H), 3.15-3.40 (m, 6H), 3.545-3.54 (m, 2H), 3.57-3.67 (m, 4H), 4.44 (s, 2H), 5.39 (br s, 1H), 7.40 (d, J=8.4 Hz, 2H), 7.43-7.59 m, 6H), 7.82 (d, J=7.8 Hz, 3H), 7.93 (d, J=7.0 Hz, 1H), 8.22 (s, 1H).

Workup

  1. temperaturethe reaction was heated to reflux
  2. temperatureAfter 90 minutes the reaction was cooled
  3. washThe reaction was washed with water (30 mL)
  4. customthe organic layer separated
  5. washwashed with dichloromethane (2×25 mL)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography
  10. washeluting 3% methanol in dichloromethane

Sources & evidence

ORD record
ord-2c11d74526b54eb9a30c69da6feff2a8
Source dataset
uspto-grants-2008_07
Patent number
US07396834B2

Reaction notes

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