Sodium Carbonate → (rac.)-(1R*,5S*)-3-(4-Hydroxy-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic Acid 8-tert-butyl Ester 2-methyl Ester

HRID 2428176Notes

Reaction equation

HRID 2428176 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C@@H:6]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:9]([CH2:10][C:11]=1OS(C(F)(F)F)(=O)=O)[CH2:8][CH2:7]2)=[O:4].[OH:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[C@@H:6]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:9]([CH2:10][C:11]=1[C:32]1[CH:33]=[CH:34][C:29]([OH:28])=[CH:30][CH:31]=1)[CH2:8][CH2:7]2)=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 131728966(rac.)-(1R*,5S*)-3-Trifluoromethanesulfonyloxy-8-aza-bicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic Acid 8-tert-butyl Ester 2-methyl Ester

Product 1

HCID 131728967(rac.)-(1R*,5S*)-3-(4-Hydroxy-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic Acid 8-tert-butyl Ester 2-methyl EsterYield 89%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a sol. of compound A1 (10.0 g, 24.1 mmol) and 4-hydroxybenzeneboronic acid (3.42 g, 24.1 mmol) in DME (171 mL) was added aq. 2 M Na2CO3 (86 mL). The mixture was stirred at rt for a few minutes, and Pd(PPh3)4 (1.39 g, 1.20 mmol) was added. The mixture was heated rapidly to 80° C., and stirred at this temperature for 60 min. The mixture was partitioned between EtOAc and water, and the aq. layer was extracted with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc 6:4) yielded the title compound (7.70 g, 89%). LC-MS: tR=0.95 min, ES+: 360.18.

Workup

  1. temperatureThe mixture was heated rapidly to 80° C.
  2. stirringstirred at this temperature for 60 min
  3. customThe mixture was partitioned between EtOAc and water
  4. extractionthe aq. layer was extracted with EtOAc
  5. dry with materialextracts were dried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were removed under reduced pressure
  8. customPurification of the crude by FC (heptane/EtOAc 6:4)

Sources & evidence

ORD record
ord-aa0c3881530e45b891d634386c3fc0d6
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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