Tetrahydrofuran → Methyl N-{[(1-tert-butoxycarbonylpiperidin-4-yl)amino]carbonyl}valinate

HRID 1867594Notes

Reaction equation

HRID 1867594 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.Cl.[CH3:23][O:24][C:25](=[O:31])[CH:26]([CH:28]([CH3:30])[CH3:29])[NH2:27].[O:32]1CCC[CH2:33]1>>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([NH:1][C:33]([NH:27][C@H:26]([C:25]([O:24][CH3:23])=[O:31])[CH:28]([CH3:30])[CH3:29])=[O:32])[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471Triethylamine2×HCID 12682914-Amino-1-Boc-piperidineHCID 12498813Valine, methyl ester, hydrochloride (1:1)

Product 1

HCID 68565788Methyl N-{[(1-tert-butoxycarbonylpiperidin-4-yl)amino]carbonyl}valinate

Procedure

4-Amino-1-boc-piperidine (205 mg, 1.02 mmol) and triethylamine (0.143 μL, 1.02 mmol) in tetrahydrofuran (5 mL) were added to a solution of p-nitrophenylchloroformate (206 mg, 1.02 mmol) in tetrahydrofuran (15 mL) at 0° C. After 1 h, additional triethylamine was added (0.286 mL, 2.04 mmol) along with DL-valine methyl ester hydrochloride (134 mg, 1.02 mmol). The reaction warmed to ambient temperature and was then heated to 50° C. After 2 h, the mixture was filtered, concentrated and redissolved in ethyl acetate. The ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine, and dried over sodium sulfate. Purification by silica gel chromatography (100% dichloromethane→7% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (300 mg). MS 358.28 (M+1)

Workup

  1. temperaturewas then heated to 50° C
  2. waitAfter 2 h
  3. filtrationthe mixture was filtered
  4. concentrationconcentrated
  5. dissolutionredissolved in ethyl acetate
  6. washThe ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine
  7. dry with materialdried over sodium sulfate
  8. customPurification by silica gel chromatography (100% dichloromethane→7% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record
ord-cdbc270fb1614c54b58ea763a178f7c2
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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