Cesium carbonate → 6-(2-tert-Butoxycarbonylamino-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester

HRID 556352Notes

Reaction equation

HRID 556352 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18](Cl)[N:17]=3)=[CH:14][C:9]=2[O:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C:71]([O:75][C:76](=[O:78])[NH2:77])([CH3:74])([CH3:73])[CH3:72]>O1CCOCC1.O.CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:77][C:76]([O:75][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:78])[N:17]=3)=[CH:14][C:9]=2[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonate2×HCID 77922tert-Butyl carbamate2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 866266246-(2-Chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester

Product 1

HCID 669929556-(2-tert-Butoxycarbonylamino-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 1.4 g (4.3 mMol) 6-(2-chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester (Step 4.1) in 32 ml dioxane is degassed repeatedly by evaporation and flushing with N2. Then 2.1 g (6.44 mMol) Cs2CO3, 77 mg (0.13 mMol) 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.3 mg (0.0429 mMol) tris(dibenzylidenaceton)dipalladium(0) and 603 mg (5.15 mMol) carbamic acid tert-butyl ester are added successively. After 4.5 h stirring at 110° C., the mixture is cooled to rt and another 77 mg 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.7 mg tris(dibenzylidenaceton)dipalladium(0), 603 mg carbamic acid tert-butyl ester and 2.1 g Cs2CO3 are added and stirring is continued for 5 h. Then the cooled mixture is poured into EtOAc and water, the aq. layer separated off and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated together with 8 g SiO2. The resulting powder is put on top of a chromatography column (SiO2; CH2Cl2) and the title compound eluted with CH2Cl2→CH2Cl2/EtOAc 4:1: MS: [M+1]+=401; HPLC: tRet=15.4.

Workup

  1. customflushing with N2
  2. temperaturethe mixture is cooled to rt
  3. stirringstirring
  4. waitis continued for 5 h
  5. customthe aq. layer separated off
  6. extractionextracted with EtOAc
  7. washThe organic layers are washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated together with 8 g SiO2
  10. washthe title compound eluted with CH2Cl2→CH2Cl2/EtOAc 4:1

Sources & evidence

ORD record
ord-474e7e7f5a7e4ebb9a8172a203656398
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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