Potassium Carbonate → tert-butyl N-tert-butoxycarbonyl-N-[5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]carbamate

HRID 1959442Notes

Reaction equation

HRID 1959442 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[O:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:26][N:27]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.[O:34]1[C:38]2([CH2:43][CH2:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH2:39]2)[O:37][CH2:36][CH2:35]1.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.C(Cl)Cl.Cl[Pd]Cl>[C:11]([O:10][C:9]([N:8]([C:5]1[C:4]([C:23]2[O:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:26][N:27]=2)=[N:3][C:2]([C:41]2[CH2:42][CH2:43][C:38]3([O:37][CH2:36][CH2:35][O:34]3)[CH2:39][CH:40]=2)=[CH:7][N:6]=1)[C:16](=[O:17])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-eneHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 59471994Tert-butyl N-[5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate

Product 1

HCID 66744206tert-butyl N-tert-butoxycarbonyl-N-[5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]carbamateYield 65%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl N-[5-bromo-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (250 mg, 0.48 mmol), 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (128 mg, 0.48 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (3.5 mg, 0.005 mmol) and K2CO3 (133 mg, 0.96 mmol) in toluene (2 mL) and water (250.0 μL) was heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and diluted with DCM (30 ml) and water (30 ml). The layers were separated and the organic layer was washed with 1M NaOH solution, dried (Na2SO4), filtered and concentrated. The crude material was purified via silica gel column chromatography using 0-30% EtOAc/Hexanes to obtain tert-butyl N-tert-butoxycarbonyl-N-[5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]carbamate (180 mg, 65%) as a yellow solid. LC/MS m/z 478.26 [M+H-Boc]+.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with 1M NaOH solution
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via silica gel column chromatography

Sources & evidence

ORD record
ord-fef057ecc04d407886720861186433f3
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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