tert-Butyl acrylate → (1R*,5S*,6RS)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one

HRID 1017272Notes

Reaction equation

HRID 1017272 reaction equation
[Br-].C([N+]1C=CC=C(O)C=1C1C=CC=CC=1)C1C=CC=CC=1.C(OC(C)(C)C)(=O)C=C.C([O-])(O)=O.[Na+].[CH2:36]([N:43]1[C@@H:48]2[C@H:49]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:50][C@@:44]1([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:45](=[O:58])[CH:46]=[CH:47]2)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N1[C@@H]2[C@@H](C(OC(C)(C)C)=O)C[C@@]1(C1C=CC=CC=1)C(=O)C=C2)C1C=CC=CC=1>O1CCOCC1.C(N(CC)CC)C>[CH2:36]([N:43]1[C@@H:48]2[CH:49]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:50][C@@:44]1([C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)[C:45](=[O:58])[CH:46]=[CH:47]2)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

8

Reactant 5

HCID 15458tert-Butyl acrylateHCID 516892Sodium BicarbonateHCID 21931695N-benzyl-3-hydroxy-2-phenylpyridinium bromideHCID 69890253(1R*,5S*,6S*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-oneHCID 69890867(1R*,5S*,6R*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one

Product 1

HCID 69890903(1R*,5S*,6RS)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-benzyl-3-hydroxy-2-phenylpyridinium bromide (255 g, 0.745 mol), tert-butyl acrylate (470 ml), triethylamine (150 ml) and 1,4-dioxane (1 l) was heated at reflux for 15 hours and cooled to room temperature. The reaction mixture was poured onto saturated aqueous NaHCO3 (1 l) and extracted into an 1:1 mixture of iso-hexane:diethyl ether (3×500 ml). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (750 g, iso-hexane:diethyl ether 0-20%) to give a 2:1 mixture of (1R*,5S*,6R*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one and (1R*,5S*,6S*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]oct-3-en-2-one (205 g, 70%) as a yellow-orange foam. The isomers were separated on silica gel (iso-hexane:diethyl ether) and crystallised from iso-hexane:diethyl ether giving yellow rhombs:

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 15 hours
  3. extractionextracted into an 1:1 mixture of iso-hexane
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (750 g, iso-hexane:diethyl ether 0-20%)
  7. customto give
  8. customThe isomers were separated on silica gel (iso-hexane:diethyl ether)
  9. customcrystallised from iso-hexane

Sources & evidence

ORD record
ord-e35e98970b2f439dac201b4898831716
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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