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 2428171Notes

Reaction equation

HRID 2428171 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[CH3:7][O:8][C:9]([C:11]1[C@@H:12]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:15]([CH2:16][C:17]=1OS(C(F)(F)F)(=O)=O)[CH2:14][CH2:13]2)=[O:10].[OH:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1>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>[CH3:7][O:8][C:9]([C:11]1[C@@H:12]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:15]([CH2:16][C:17]=1[C:38]1[CH:39]=[CH:40][C:35]([OH:34])=[CH:36][CH:37]=1)[CH2:14][CH2:13]2)=[O:10]

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 83%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Aq. 2M Na2CO3 (90.0 mL) was added to a mixture of compound A1 (10.1 g, 24.4 mmol) and 4-hydroxybenzeneboronic acid (3.37 g, 24.4 mmol) in DME (180 mL). The mixture was degassed with N2 for 3 min, and Pd(PPh3)4 (1.42 g, 1.23 mmol) was added. The mixture was heated quickly to 80° C., and stirred at this temperature for 1 h. The mixture was allowed to cool to rt, and was partitioned between EtOAc (250 mL) and water (250 mL). The org. phase was washed with water. The combined aq. layers were 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 (EtOAc/heptane 1:1) yielded the title compound (7.27 g, 83%). LC-MS: tR=0.94 min; ES+: 360.29.

Workup

  1. customThe mixture was degassed with N2 for 3 min
  2. temperatureto cool to rt
  3. customwas partitioned between EtOAc (250 mL) and water (250 mL)
  4. washphase was washed with water
  5. extractionThe combined aq. layers were extracted with EtOAc
  6. dry with materialextracts were dried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customPurification of the crude by FC (EtOAc/heptane 1:1)

Sources & evidence

ORD record
ord-d4969ca16949466c8efe6cc0999c22cf
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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