tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(6-chloro-2-methoxypyridin-3-yl)piperazine-1-carboxylate

HRID 2209271Notes

Reaction equation

HRID 2209271 reaction equation
Br[C:2]1[C:3]([O:9][CH3:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:5]1[N:4]=[C:3]([O:9][CH3:10])[C:2]([N:14]2[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]2)=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 532174543-Bromo-6-chloro-2-methoxypyridine

Product 1

HCID 117843574Tert-butyl 4-(6-chloro-2-methoxypyridin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

3-bromo-6-chloro-2-methoxypyridine (1.15 g, 5.17 mmol), tert-butyl piperazine-1-carboxylate (900 mg, 4.8 mmol), sodium tert-butoxide (1.39 g, 14.5 mmol), Pd2(dba)3 (130 mg, 0.15 mmol) and XantPhos (250 mg, 0.44 mmol) were taken up in toluene (36 mL) under Ar. The reaction mixture was heated to 70° C. and was stirred for 18 h. The mixture was cooled and partitioned between water and EtOAc. The phases were separated, and the organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (0-3% Et2O in DCM) to afford tert-butyl 4-(6-chloro-2-methoxypyridin-3-yl)piperazine-1-carboxylate 7.10. LCMS-ESI+ (m/z): [M+H]+ calcd for C15H23ClN3O3: 328.1; found: 328.3.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between water and EtOAc
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica gel chromatography (0-3% Et2O in DCM)

Sources & evidence

ORD record
ord-82a880b07aa64e04a1cb84a1c0414e8e
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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