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

HRID 469907Notes

Reaction equation

HRID 469907 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:14][C:13](=[O:15])[C@@H:12]2[C@H:10]1[C@H:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[CH:35](N(C)C)[N:36]([CH3:38])[CH3:37])(C)(C)C.C(OCC)C.CCCCCC>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:14](=[CH:35][N:36]([CH3:38])[CH3:37])[C:13](=[O:15])[C@@H:12]2[C@H:10]1[C@H:11]2[C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8058HexaneHCID 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 97.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of di-tert-butyl (1S,2S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (15.15 g, 36.82 mmol, See WO03/104217/A2 for synthesis details) in toluene (90.90 mL) is added tert-butoxybis(dimethylamino)methane (12.83 g, 73.63 mmol). This mixture is then heated to 80° C. for 1 hour and then allowed to cool to ambient temperature. The solvent volume is reduced to about 35 ml. The mixture is stirred while diethyl ether and hexane are added to cause a precipitate to form. The solids are collected by filtration, washed with hexanes, and air dried to obtain the title compound (16.7 g, 35.79 mmol, 97.2% yield). MS (m/z): 467.2 (M+H).

Workup

  1. temperatureto cool to ambient temperature
  2. additionare added
  3. customto form
  4. filtrationThe solids are collected by filtration
  5. washwashed with hexanes, and air
  6. customdried

Sources & evidence

ORD record
ord-07090cd61a4747b5a12643203b1ab81a
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

Loading…