Triethylamine → N-Boc-3-mesyloxypiperidine

HRID 1898969Notes

Reaction equation

HRID 1898969 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][S:23]([CH3:22])(=[O:25])=[O:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 5456991-Boc-3-hydroxypiperidine

Product 1

HCID 568122N-Boc-3-mesyloxypiperidineYield 96.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of the title compound of Example 1 (44.3 g, 220 mmol) and Et3N (61.4 mL, 440 mmol, 2 eq) in THF (250 mL) was added dropwise at rt (maintained by cooling from an ice bath), methanesulfonyl chloride (27.77 g, 242 mmol, 1.1 eq). The reaction mixture was stirred for 1 h at rt when TLC (solvent system C) indicated completion. The precipitated Et3N·HCl was removed by filtration and the filter cake was washed with 50 mL of THF. The combined filtrate and washings were evaporated in vacuo to give the crude product as a yellow oil. This was dissolved in EtOAc/hexanes (1:2) and passed through a pad of silica gel eluting with ethyl acetate/hexanes (1:3). Evaporation of the filtrate afforded the product as a pale yellow oil (59.1 g, 96%) which crystallized on standing. Recrystallization from EtOAc/hexane (1:10) afforded an analytically pure sample: mp 69°-70° C.; 1H-NMR (CDCl3) ∂4.72 (m, 1H), 3.63 (m, 2H), 3.46 (m, 1H), 3.32 (m, 1H), 3.05 (s, 3H), 1.75-2.06 (complex m, 4H), 1.46 (s, 9H); CIMS (MH+ calcd for C11H21NO5S): 280. Found (MH+): 280; Anal. (calcd for C11H21NO5S): C, H, N.

Workup

  1. customThe precipitated Et3N·HCl was removed by filtration
  2. washthe filter cake was washed with 50 mL of THF
  3. customThe combined filtrate and washings were evaporated in vacuo
  4. customto give the crude product as a yellow oil
  5. customEvaporation of the filtrate

Sources & evidence

ORD record
ord-ec7ba9972db34c61a6713450761ad187
Source dataset
uspto-grants-1996_11
Patent number
US05571832

Reaction notes

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