Potassium tert-butoxide → HCID 136436908, compound

HRID 990227Notes

Reaction equation

HRID 990227 reaction equation
[CH3:1][C:2](C)([O-:4])[CH3:3].[K+].[CH2:7]([C:9]1[N:10]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)[N:11]=[C:12]2[C:17](=[O:18])[NH:16][C:15]([C:19]3[C:20](OCCC)=[N:21][CH:22]=[C:23]([S:25]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)(=[O:27])=[O:26])[CH:24]=3)=[N:14][C:13]=12)[CH3:8]>CC(O)C>[CH2:7]([C:9]1[N:10]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)[N:11]=[C:12]2[C:17](=[O:18])[NH:16][C:15]([C:19]3[C:20]([O:4][CH:2]([CH3:3])[CH3:1])=[N:21][CH:22]=[C:23]([S:25]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)(=[O:26])=[O:27])[CH:24]=3)=[N:14][C:13]=12)[CH3:8]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 136436909HCID 136436909, compound

Product 1

HCID 136436908HCID 136436908, compoundYield 35.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Potassium t-butoxide (290 mg, 2.60 mmol) was added to a stirred solution of the title compound of Example 20 (239 mg, 0.43 mmol) in propan-2-ol (7 ml) under nitrogen and the reaction mixture heated under reflux for 48 hours, then allowed to cool. The resulting mixture was evaporated under reduced pressure and the residue partitioned between water (20 ml) and ethyl acetate (20 ml). The phases were separated, the aqueous phase extracted with ethyl acetate and the combined organic solutions dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, using an elution gradient of dichloromethane: methanol (100:0 to 95:5), to afford the title compound (84 mg, 35%) as a foam. δ (CDCl3): 1.28 (3H, t), 1.56 (6H, 2×d), 2.28 (3H, s), 2.50 (4H, m), 3.04 (2H, q), 3.14 (4H, m), 5.68 (3H, m), 7.09 (1H, d), 7.22 (1H, m), 7.62 (1H, m), 8.57 (1H, d), 8.62 (1H, s), 9.02 (1H, s), 10.68 (1H, s). LRMS: m/z 553 (M+1)+.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for 48 hours
  3. temperatureto cool
  4. customThe resulting mixture was evaporated under reduced pressure
  5. customthe residue partitioned between water (20 ml) and ethyl acetate (20 ml)
  6. customThe phases were separated
  7. extractionthe aqueous phase extracted with ethyl acetate
  8. dry with materialthe combined organic solutions dried (MgSO4)
  9. customevaporated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-e94c21acf01548d29ab7ac3ed99f3e23
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Reaction notes

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