Triethylamine → tert-Butyl trans-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]-5-[(methylsulfonyl)oxy]piperidine-1-carboxylate

HRID 602452Notes

Reaction equation

HRID 602452 reaction equation
[OH:1][CH:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:5]([CH2:15][C:16]2([OH:22])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>ClCCl>[OH:22][C:16]1([CH2:15][C@H:5]2[CH2:4][CH2:3][C@H:2]([O:1][S:31]([CH3:30])(=[O:33])=[O:32])[CH2:7][N:6]2[C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67270791HCID 67270791, compound

Product 1

HCID 86624146tert-Butyl trans-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]-5-[(methylsulfonyl)oxy]piperidine-1-carboxylateYield 28.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 5-hydroxy-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate (1.92 g, 6.09 mmol, step 2 of Example 2), triethylamine (739 mg, 7.30 mmol) in dichloromethane (27 mL) was added methanesulfonyl chloride (836 mg, 7.30 mmol) at 0° C., and the mixture was allowed to warm to room temperature over 20 h. The mixture was quenched with water (50 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (50 mL×3). The combined organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:5) to give 673 mg (28%) of the title compound as a white crystal. (cis isomer, 634 mg, 26% yield)

Workup

  1. customThe mixture was quenched with water (50 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with dichloromethane (50 mL×3)
  4. dry with materialThe combined organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:5)

Sources & evidence

ORD record
ord-7b8b8b922287408d85ae8e9b4fb0bdf3
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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