tert-Butoxy bis(dimethylamino)methane → Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-(dimethylaminomethylene)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 469919Notes

Reaction equation

HRID 469919 reaction equation
C(O[CH:6](N(C)C)[N:7]([CH3:9])[CH3:8])(C)(C)C.[C:13]([O:17][C:18]([NH:20][C@@:21]1([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:26][C:25](=[O:27])[C@@H:24]2[C@H:22]1[C@H:23]2[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:19])([CH3:16])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1.C(OC)(C)(C)C.CCCCCC>[C:13]([O:17][C:18]([NH:20][C@@:21]1([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:26](=[CH:6][N:7]([CH3:9])[CH3:8])[C:25](=[O:27])[C@@H:24]2[C@H:22]1[C@H:23]2[C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 2

HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 59712878Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-oxo-, 2,6-bis(1,1-dimethylethyl) ester, (1S,2S,5R,6R)-

Product 1

HCID 86665754Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-(dimethylaminomethylene)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 91.1%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
80 °C

Procedure

Tert-butoxybis(dimethylamino)methane (481.1 ml, 2.33 mol) is added to a suspension of di-tert-butyl(1S,2S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (600 g, 1.46 mol) in dry toluene (3.6 L) at room temperature under nitrogen. The mixture is heated at 80° C. for 3 hour and 45 minutes, then cooled to room temperature and stirred overnight. The reaction volume is reduced in vacuo, diluted with methyl tert-butyl ether (1.8 L) and hexane (1.8 L), and stirred for 3 hours at 15° C. After 3 hours, the resulting solid is collected by filtration, washed with cold hexane (2×1.8 L), and dried under vacuum to obtain the title compound (620.4 g, yield 91%). HPLC-MS: 98%.

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred for 3 hours at 15° C
  3. waitAfter 3 hours
  4. filtrationthe resulting solid is collected by filtration
  5. washwashed with cold hexane (2×1.8 L)
  6. customdried under vacuum

Sources & evidence

ORD record
ord-5f7ad3a80c9748b88df056ebdc271c8b
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

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