Cesium carbonate → HCID 71003668, compound

HRID 715979Notes

Reaction equation

HRID 715979 reaction equation
[NH:1]1[CH2:4][CH2:3][C@@H:2]1[CH2:5][O:6][C:7]1[C:19](Br)=[CH:18][CH:17]=[C:16]([NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C:8]=1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:25]([O:24][C:22]([NH:21][C:16]1[CH:17]=[CH:18][C:19]2[N:1]3[CH2:4][CH2:3][C@@H:2]3[CH2:5][O:6][C:7]=2[C:8]=1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 70983327HCID 70983327, compound2×

Product 1

HCID 71003668HCID 71003668, compoundYield 11.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 2-((R)-1-azetidin-2-ylmethoxy)-6-benzyloxycarbonylamino-3-bromo-benzoate (Intermediate 46, 1.46 g), palladium acetate (0.167 g), cesium carbonate (1.935 g) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.925 g) in toluene (35 mL) was stirred and heated at 100° C. under nitrogen for 4 hours. After cooling, the mixture was diluted with ethyl acetate and water and filtered through celite. The organic layer was separated, dried (Na2SO4) and filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-40% to give tert-butyl (R)-6-benzyloxycarbonylamino-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta[a]naphthalene-5-carboxylate (0.141 g) as an off-white solid.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered through celite
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified by chromatography on silica
  8. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-40%

Sources & evidence

ORD record
ord-fe52507a366a46aca064dde19ab7b64e
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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