Tetrahydrofuran → 3-(2-Benzyloxy-3-cyanophenyl)-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester

HRID 600641Notes

Reaction equation

HRID 600641 reaction equation
[CH2:1]([O:8][C:9]1[C:16](Br)=[CH:15][CH:14]=[CH:13][C:10]=1[C:11]#[N:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]([O:22][C:23]([N:25]1[CH:30]2[CH2:31][CH2:32][CH:26]1[CH:27]=[C:28](B1OC(C)(C)C(C)(C)O1)[CH2:29]2)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:18]([O:22][C:23]([N:25]1[CH:30]2[CH2:31][CH2:32][CH:26]1[CH:27]=[C:28]([C:16]1[CH:15]=[CH:14][CH:13]=[C:10]([C:11]#[N:12])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:29]2)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 53393373Tert-butyl 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo(3.2.1)oct-2-ene-8-carboxylateHCID 598089582-(Benzyloxy)-3-bromobenzonitrile

Product 1

HCID 671520573-(2-Benzyloxy-3-cyanophenyl)-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl esterYield 64.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

To a flask was added 2-benzyloxy-3-bromobenzonitrile (1.29 g, 4.47 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester (1.50 g, 4.47 mmol), and THF (30 mL), 2.0 M sodium carbonate in water (8.95 mL), and bis(triphenylphosphine)palladium(II) chloride (78 mg, 0.11 mmol). The reaction mixture was purged with nitrogen, heated to reflux overnight, cooled to room temperature, and concentrated. The resulting solution was diluted with DCM (25 mL) and washed with water (25 mL) The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography eluting with ethyl acetate in hexanes (0-50%) to give partially purified product (1.2 g). (m/z): [M+H]+ calcd for C26H28N2O3 416.21; (-tert-butyl 361.2); found 361; (-Boc 317.2); found 317.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux overnight
  4. concentrationconcentrated
  5. additionThe resulting solution was diluted with DCM (25 mL)
  6. washwashed with water (25 mL) The organic layer
  7. customwas collected
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by flash column chromatography
  12. washeluting with ethyl acetate in hexanes (0-50%)

Sources & evidence

ORD record
ord-0b6539430eb54477b1207d42beb63c7d
Source dataset
uspto-grants-2011_03
Patent number
US07902220B2

Reaction notes

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