Triethylamine → Tert-butyl (1-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)isoxazol-5-YL)cyclopropyl)carbamate

HRID 1772374Notes

Reaction equation

HRID 1772374 reaction equation
Br[C:2]1[C:3]([CH3:18])=[N:4][O:5][C:6]=1[C:7]1([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:9][CH2:8]1.[CH3:19][C:20]1([CH3:27])[C:24]([CH3:26])([CH3:25])[O:23][BH:22][O:21]1.C(N(CC)CC)C>CC#N.CC#N.Cl[Pd]Cl.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O1CCOCC1>[CH3:18][C:3]1[C:2]([B:22]2[O:23][C:24]([CH3:26])([CH3:25])[C:20]([CH3:27])([CH3:19])[O:21]2)=[C:6]([C:7]2([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:9][CH2:8]2)[O:5][N:4]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 67951107tert-Butyl (1-(4-bromo-3-methylisoxazol-5-yl)cyclopropyl)carbamate

Product 1

HCID 67814800Tert-butyl (1-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)isoxazol-5-YL)cyclopropyl)carbamateYield 100%

Reagents, catalysts & solvents 3

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 50 mL round bottom flask containing tert-butyl 1-(4-bromo-3-methylisoxazol-5-yl)cyclopropylcarbamate (0.219 g, 0.621 mmol) was added dichlorobis(acetonitrile)palladium(II) (0.0025 g, 9.64 μmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.0134 g, 0.033 mmol), followed by anhydrous 1,4-dioxane (0.40 mL). The reaction vessel was evacuated and purged with N2 (g) (3×). To the flask was added 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.153 mL, 1.056 mmol) and triethylamine (0.294 mL, 2.113 mmol) sequentially. The reaction vessel was evacuated and purged with N2 (g) again, then heated to 100° C. The reaction mixture became heterogeneous and was judged complete within 1 h by LC-MS. The heterogeneous mixture was cooled to room temperature, dilute with EtOAc and the mixture was filtered over a plug of Celite. The filter cake was rinsed with EtOAc (3×) and the filtrate was concentrated to give a yellow oil, that crystallized upon standing under vacuum. The product tert-butyl 1-(3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)cyclopropylcarbamate (0.226 g, 0.620 mmol, 100% yield) was used without further purification. LC/MS m/z 365 [M+H]+.

Workup

  1. customThe reaction vessel was evacuated
  2. custompurged with N2 (g) (3×)
  3. customThe reaction vessel was evacuated
  4. custompurged with N2 (g) again
  5. temperatureThe heterogeneous mixture was cooled to room temperature
  6. additiondilute with EtOAc
  7. filtrationthe mixture was filtered over a plug of Celite
  8. washThe filter cake was rinsed with EtOAc (3×)
  9. concentrationthe filtrate was concentrated
  10. customto give a yellow oil, that
  11. customcrystallized

Sources & evidence

ORD record
ord-b7e7879a7443486aacf3959047b49519
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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