Water → Benzyl 4-(4-(chloromethyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 517560Notes

Reaction equation

HRID 517560 reaction equation
O1CCCCC1O[CH2:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:17][CH2:16]2)[CH:10]=1.S(Cl)([Cl:33])=O.O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:33][CH2:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:17][CH2:16]2)[CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 86711499benzyl 4-(4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 86711500Benzyl 4-(4-(chloromethyl)pyridin-2-yl)piperazine-1-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 4-(4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridin-2-yl)piperazine-1-carboxylate (7.3 g, 17.7 mmol) in DCM (30 mL), thionyl chloride (7.7 mL, 106.6 mmol) was added slowly at RT, followed by the addition of H2O (0.05 mL). The mixture was stirred at RT overnight, poured into a solution of aqueous NaHCO3 (sat., 50 mL), and extracted with DCM (2×30 mL). The combined organic layers were washed with H2O (50 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by silica gel column chromatography (Petroleum ether:EtOAc=3:1) to give benzyl 4-(4-(chloromethyl)pyridin-2-yl)piperazine-1-carboxylate as a yellow solid (5.0 g, 82%). MS (ES+) C18H20ClN3O2 requires: 345, found: 346 [M+H]+.

Workup

  1. extractionextracted with DCM (2×30 mL)
  2. washThe combined organic layers were washed with H2O (50 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford the crude product, which
  7. customwas purified by silica gel column chromatography (Petroleum ether:EtOAc=3:1)

Sources & evidence

ORD record
ord-9cfdcba404f049d4a1eb7c895fafdf2f
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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