Triethylamine → HCID 58386787, compound

HRID 1920175Notes

Reaction equation

HRID 1920175 reaction equation
O[C@@H:2]1[CH2:7][C@@H:6]([O:8][CH3:9])[CH2:5][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:3]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:32]=[N+:33]=[N-:34].[Na+]>ClCCl.CCOC(C)=O.CN(C=O)C>[N:32]([C@H:2]1[CH2:7][C@@H:6]([O:8][CH3:9])[CH2:5][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:3]1)=[N+:33]=[N-:34]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 58386825HCID 58386825, compound

Product 1

HCID 58386787HCID 58386787, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (3R,5R)-benzyl 3-hydroxy-5-methoxypiperidine-1-carboxylate (1 eq) in 40 mL of dichloromethane was added triethyl amine (3 eq) and methanesulfonyl chloride (1.5 eq) at 0° C. The reaction mixture was allowed to stir at room temperature for 2 hours. The crude mixture was diluted with 150 mL of EtOAc, washed with sat. aq. sodium bicarbonate, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=1:1) to give the intermediate, which was dissolved in 15 mL of DMF. Sodium azide (3.3 eq) was added and the resulting suspension was stirred at 80° C. overnight. The reaction mixture was diluted with 150 mL of EtOAc, washed with water, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=1:2) to yield (3S,5R)-benzyl 3-azido-5-methoxypiperidine-1-carboxylate (95%). LC/MS (m/z): 263.2 (MH+-28).

Workup

  1. washwashed with sat. aq. sodium bicarbonate, brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by flash chromatography (EtOAc:hexanes=1:1)
  6. customto give the intermediate, which
  7. stirringthe resulting suspension was stirred at 80° C. overnight
  8. washwashed with water, brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was purified by flash chromatography (EtOAc:hexanes=1:2)

Sources & evidence

ORD record
ord-de8894f74d0d4ee3bc88000649148e47
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

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