Triethylamine → Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 469908Notes

Reaction equation

HRID 469908 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:14](=[CH:15]N(C)C)[C:13](=[O:19])[C@@H:12]2[C@H:10]1[C@H:11]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[H-].C([Al+]CC(C)C)C(C)C.[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:14](=[CH2:15])[C:13](=[O:19])[C@@H:12]2[C@H:10]1[C@H:11]2[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 86665754Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-(dimethylaminomethylene)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 67643282Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-(dimethylaminomethylene)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (15.7 g, 33.8 mmol) in tetrahydrofuran (340 ml) is added triethylamine (6.6 mL, 47.32 mmol). The mixture is cooled to −78° C. Diisobutylaluminium hydride (1N in toluene, 50 mL, 50 mmol) is added over one hour. The mixture is stirred for two additional hours. Then add 30 mL of saturated aqueous ammonium chloride. The mixture is allowed to warm to ambient temperature. The mixture is transferred to a separatory funnel and washed with brine. The organic layer is dried over MgSO4, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by flash chromatography (0 to 50% ethyl acetate/hexanes) to give the title compound (12 g, 33.34 mmol, 83.8% yield). MS (m/z): 422 (M−H).

Workup

  1. temperatureto warm to ambient temperature
  2. customThe mixture is transferred to a separatory funnel
  3. washwashed with brine
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a residue
  8. customThe residue is purified by flash chromatography (0 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8f6fdfd0f008454389db3a3f93a8416c
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

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