1-Hydroxybenzotriazole → (2S,5R)-N-(2-tert-Butoxycarbonylaminoethoxy)-5-(benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxamide

HRID 711003Notes

Reaction equation

HRID 711003 reaction equation
[CH2:1]([O:8][NH:9][C@H:10]1[CH2:15][N:14]([C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[C@H:13]([C:22]([OH:24])=O)[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][O:26][CH2:27][CH2:28][NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[C:32]([O:31][C:30]([NH:29][CH2:28][CH2:27][O:26][NH:25][C:22]([C@@H:13]1[CH2:12][CH2:11][C@@H:10]([NH:9][O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:15][N:14]1[C:16](=[O:21])[C:17]([F:20])([F:18])[F:19])=[O:24])=[O:36])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15610443tert-butyl N-(2-(aminooxy)ethyl)carbamateHCID 87217278(2S,5R)-5-(Benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylic acid

Product 1

HCID 117987976(2S,5R)-N-(2-tert-Butoxycarbonylaminoethoxy)-5-(benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxamideYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2S,5R)-5-(Benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylic acid (0.879 g, 2.54 mmol) described in Example 98 and tert-butyl 2-(aminooxy)ethylcarbamate (0.559 g) of Reference Example 9 were dissolved in N,N-dimethylformamide (11 mL), and to which was added 1-hydroxybenzotriazole.monohydrate (0.489 g), followed by ice-cooling. To this was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.613 g), and the temperature was elevated to room temperature, followed by reacting for 3 h. Water was added to the reacted 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, 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 1.07 g of the title compound (yield 84%).

Workup

  1. temperaturecooling
  2. customwas elevated to room temperature
  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-02046ab83e9040a496d96e84aac723d4
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

Loading…