1-Hydroxybenzotriazole → (2S,5R)-N-(2-tert-Butoxycarbonylaminoethoxy)-5-(benzyloxyamino)-1-[2-(trimethylsilyl)ethyloxycarbonyl]piperidine-2-carboxamide

HRID 711005Notes

Reaction equation

HRID 711005 reaction equation
[CH2:1]([O:8][NH:9][C@H:10]1[CH2:15][N:14]([C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])=[O:17])[C@H:13]([C:25]([OH:27])=O)[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:28][O:29][CH2:30][CH2:31][NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[C:35]([O:34][C:33]([NH:32][CH2:31][CH2:30][O:29][NH:28][C:25]([C@@H:13]1[CH2:12][CH2:11][C@@H:10]([NH:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:15][N:14]1[C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:22])[CH3:23])=[O:17])=[O:27])=[O:39])([CH3:38])([CH3:36])[CH3:37]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15610443tert-butyl N-(2-(aminooxy)ethyl)carbamateHCID 131733975(2S,5R)-5-((Benzyloxy)amino)-1-(2-trimethylsilylethoxycarbonyl)piperidine-2-carboxylic acid

Product 1

HCID 131733976(2S,5R)-N-(2-tert-Butoxycarbonylaminoethoxy)-5-(benzyloxyamino)-1-[2-(trimethylsilyl)ethyloxycarbonyl]piperidine-2-carboxamideYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2S,5R)-5-(Benzyloxyamino)-1-((2-(trimethylsilyl)ethoxy)carbonyl)piperidine-2-carboxylic acid (601 mg, 1.52 mmol) described in Example 101 and tert-butyl 2-(aminooxy)ethylcarbamate (303 mg, 1.72 mmol) of Reference Example 9 were dissolved in N,N-dimethylformamide (5.8 mL), to which was added 1-hydroxybenzotriazole.monohydrate (264 mg), followed by ice cooling. To this was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (330 mg), a temperature was elevated to room temperature, followed by reaction for 5 h. Water was added to the reaction mixture and extracted with ethyl acetate. After the organic layer was washed with 10% citric acid aqueous solution, water, 6.5% sodium bicarbonate aqueous solution and saturated brine sequentially, the organic layer was dehydrated over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting oil residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/2) to afford 450 mg of the title compound (yield 54%).

Workup

  1. customwas elevated to room temperature
  2. customfollowed by reaction for 5 h
  3. extractionextracted with ethyl acetate
  4. washAfter the organic layer was washed with 10% citric acid aqueous solution, water, 6.5% sodium bicarbonate aqueous solution and saturated brine sequentially
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resulting oil residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-8a5ef133b3d74fd08da25624e4142a69
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

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