Triethylamine → cis (+/-)-Benzyl 3-(tert-butoxycarbonylamino)-5-(fluoromethyl)piperidine-1-carboxylate

HRID 69990Notes

Reaction equation

HRID 69990 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C@@H:13]([CH2:15]O)[CH2:12][N:11]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:27]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.C(N(CC)CC)C>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C@@H:13]([CH2:15][F:27])[CH2:12][N:11]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 67814Perfluoro-1-butanesulfonyl fluorideHCID 131729683HCID 131729683, compound

Product 1

HCID 131729687cis (+/-)-Benzyl 3-(tert-butoxycarbonylamino)-5-(fluoromethyl)piperidine-1-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(hydroxymethyl)piperidine-1-carboxylate (1 eq.), perfluorobutanesulfonylfluoride (2 eq.), triethylamine-HF (4 eq.) and triethylamine (6 eq.) in tetrahydrofuran at a concentration of 0.16 M was stirred for 36 hours. Upon dilution with ethyl acetate (50×) the solution was washed with 1N HCl, NaHCO3(sat.) and brine, was dried over MgSO4, filtered, concentrated and purified by column chromatography (25-40% ethyl acetate/hexanes) to yield cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(fluoromethyl)piperidine-1-carboxylate (45% yield). LCMS (m/z): 267.1 (MH+); LC Rt=4.23 min.

Workup

  1. washUpon dilution with ethyl acetate (50×) the solution was washed with 1N HCl, NaHCO3(sat.) and brine
  2. dry with materialwas dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by column chromatography (25-40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1677d6cbeadb4e1eb2c04576732108f0
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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