Hydrogen Peroxide → HCID 178499264, compound

HRID 1190054Notes

Reaction equation

HRID 1190054 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16].C(B(CCCC)CCCC)CCC.C([Cu])#N.Br[CH:59]1[CH2:64][CH2:63][CH2:62][CH:61]=[CH:60]1.[OH-].[Na+].OO>C1COCC1.CCOC(C)=O>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([CH:64]2[CH2:63][CH2:62][CH2:61][CH:60]=[CH:59]2)=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:26][CH2:27][C@H:28]([CH3:31])[CH2:29][CH2:30]1)=[O:24])=[O:16]

Participants

11

Reactant 8

HCID 784Hydrogen PeroxideHCID 7912DiisopropylamineHCID 14798Sodium HydroxideHCID 31216TributylboraneHCID 1370573-BromocyclohexeneHCID 178418339ButyllithiumHCID 178418546HCID 178418546, compoundHCID 178499312HCID 178499312, compound

Product 1

HCID 178499264HCID 178499264, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

In a small RB flask THF (1.5 mL) was placed followed by diisopropylamine (80 μl, 0.57 mmol) and the mixture was cooled to −40° C. n-BuLi (1.6 M, 0.34 mL, 0.54 mmol) was added dropwise. It was stirred at this temperature for 20 min. The mixture was cooled to −78° C. and 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (200 mg, 0.47 mmol) in THF (2 mL) was added dropwise. Stirring at −78° C. was continued for 30 min. Tributyl borane (1M in ether, 0.48 mL,) was added and the mixture was allowed to come to room temperature over a period of 1 h. This solution was added to a suspension of CuCN (47 mg) in THF (1 mL) cooled to −30° C. The mixture was stirred at this temperature for 20 min. 3-Bromocyclohexene (90%, 60 μl, 0.47 mmol) was added and the mixture was allowed to come to room temperature slowly. It was stirred at this temperature for 16 h. The mixture was cooled to 0° C. and 10% NaOH (0.8 mL) was added followed by dropwise addition of 30% H2O2 (0.27 mL). The mixture was stirred for 10 min. It was diluted with EtOAc, washed with water and brine, dried (MgSO4) and evaporated. Pure 5-cyclohex-2-enyl-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester was obtained on chromatography over silica gel (hexane:EtOAc-9:1, 4:1 and 7:3 eluents) (153 mg, 64%).

Workup

  1. additionwas added dropwise
  2. stirringStirring at −78° C.
  3. waitwas continued for 30 min
  4. waitto come to room temperature over a period of 1 h
  5. temperaturecooled to −30° C
  6. stirringThe mixture was stirred at this temperature for 20 min
  7. customto come to room temperature
  8. stirringIt was stirred at this temperature for 16 h
  9. temperatureThe mixture was cooled to 0° C.
  10. stirringThe mixture was stirred for 10 min
  11. washwashed with water and brine
  12. dry with materialdried (MgSO4)
  13. customevaporated

Sources & evidence

ORD record
ord-66ab3ff86de74a539b062b4285fc09a7
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

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