Allylamine → 1-Cyclohexene-1-carboxylic acid, 3-(1-ethylpropoxy)-4-hydroxy-5-(2-propen-1-ylamino)-, ethyl ester, (3R,4S,5R)-

HRID 495684Notes

Reaction equation

HRID 495684 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH2:7][C@H:8]2[C@@H:10]([C@H:11]([O:13][CH:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:12]=1)[O:9]2)=[O:5])[CH3:2].CCOCC.[Mg+2].[Br-].[Br-].[CH2:27]([NH2:30])[CH:28]=[CH2:29].S([O-])([O-])(=O)=O.[NH4+].[NH4+]>COC(C)(C)C.C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[CH2:7][C@@H:8]([NH:30][CH2:27][CH:28]=[CH2:29])[C@H:10]([OH:9])[C@H:11]([O:13][CH:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:12]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 7853AllylamineHCID 6097028Ammonium SulfateHCID 9903262Magnesium bromide diethyl etherateHCID 10131259ethyl (1S,5R,6S)-5-(1-ethylpropoxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate

Product 1

HCID 105911371-Cyclohexene-1-carboxylic acid, 3-(1-ethylpropoxy)-4-hydroxy-5-(2-propen-1-ylamino)-, ethyl ester, (3R,4S,5R)-Yield 100.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
55 °C

Procedure

In a 2.5 l 4-necked round bottom flask equipped with a reflux condenser, a thermometer, a mechanical stirrer and an inert gas supply 254.3 g (1.0 mol) of (1S,5R,6S)-5-(1-ethyl-propoxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester were dissolved under argon with stirring in 900 ml tert.-butyl methyl ether and 100 ml acetonitrile whereby the temperature dropped to about 10° C. To the clear, yellowish solution 51.7 g (0.2 mol) of magnesium bromide diethyl etherate were added followed by 150 ml (2.0 mol) of allylamine whereby the temperature rose to about 20° C. The yellow suspension was heated to 55° C. whereby complete dissolution occurred after about 1.5 h. The clear yellow solution was refluxed for 15 h. The yellowish, turbid solution was cooled to about 30° C. and stirred vigorously with 1000 ml of 1M aqueous ammonium sulfate for 15 min whereby a clear two-phase mixture evolved after initial cloudiness. The organic phase was separated, filtered and evaporated in a rotary evaporator at 48° C./340 mbar to a volume of about 580 ml. The solid particles were filtered and the brown solution was evaporated at 48° C./340 to 15 mbar for 2 h to yield as the crude product 312.8 g (97%) of (3R,4S,5R)-5-allylamino-3-(1-ethyl-propoxy)-4-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester as a brown-yellow oil containing about 7.0% of the 4-allylamino-5-hydroxy isomer.

Workup

  1. customIn a 2.5 l 4-necked round bottom flask equipped with a reflux condenser
  2. customrose to about 20° C
  3. dissolutionwhereby complete dissolution
  4. temperatureThe clear yellow solution was refluxed for 15 h
  5. temperaturewas cooled to about 30° C.
  6. customThe organic phase was separated
  7. filtrationfiltered
  8. customevaporated in a rotary evaporator at 48° C./340 mbar to a volume of about 580 ml
  9. filtrationThe solid particles were filtered
  10. customthe brown solution was evaporated at 48° C./340 to 15 mbar for 2 h

Sources & evidence

ORD record
ord-4620671d7e2046c9acb98b4b4347e0c7
Source dataset
uspto-grants-2005_09
Patent number
US06939986B2

Reaction notes

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