Sodium Carbonate → HCID 58547379, compound

HRID 1850305Notes

Reaction equation

HRID 1850305 reaction equation
Cl[C:2]1[C:3]([CH:8]2[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:33]2[CH2:34][CH2:35][O:36][CH2:37][CH:38]=2)O1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:15]([O:14][C:12]([N:10]1[CH2:11][CH:8]([C:3]2[C:2]([C:33]3[CH2:38][CH2:37][O:36][CH2:35][CH:34]=3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:9]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 59351411Tert-butyl 3-(3-chloropyrazin-2-yl)azetidine-1-carboxylate

Product 1

HCID 58547379HCID 58547379, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-(3-chloro-pyrazin-2-yl)-azetidine-1-carboxylic acid tert-butyl ester (7) (1.0 g, 3.7 mmol) in dioxane (16 mL) was added a solution of Na2CO3 (780 mg, 6.4 mmol) in 5 mL water, followed by additional of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (114) (purchased from WUXI APPTEC) (840 mg 4.0 mmol) and Pd(dppf)Cl2 (80 mg). The resulting mixture was heated to reflux overnight under N2 atmosphere. TLC showed that the staring material was consumed completely. The solution was filtered and the filtrate was concentrated to give the residue which was purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether) to give the product 3-[3-(3,6-dihydro-2H-pyran-4-yl)-pyrazin-2-yl]-azetidine-1-carboxylic acid tert-butyl ester (115) (938 mg, 2.96 mmol, yield 80%) as solid. ESI-MS (M+1): 318 calc. for C17H23N3O3 317.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux overnight under N2 atmosphere
  3. customwas consumed completely
  4. filtrationThe solution was filtered
  5. concentrationthe filtrate was concentrated
  6. customto give the residue which
  7. customwas purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a3ef1ff9a61e41789d675652bfac15e7
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

Loading…