Benzyl chloroformate → 1-Benzyl 6-(tert-butyl) 1,6-diazaspiro[3.5]nonane-1,6-dicarboxylate

HRID 1912402Notes

Reaction equation

HRID 1912402 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH2:17])([CH2:14][CH2:15]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.Cl[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44]>ClCCl.O.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]2([N:17]([C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)=[O:44])[CH2:15][CH2:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10387Benzyl chloroformateHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58293371HCID 58293371, compound

Product 1

HCID 582933361-Benzyl 6-(tert-butyl) 1,6-diazaspiro[3.5]nonane-1,6-dicarboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Procedure

To a solution of an optically-active compound of 3-amino-3-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (6.46 g), triphenylphosphine (12.5 g) and triethylamine (13.3 ml) in dichloromethane (226 ml) cooled to 0° C. was added carbon tetrabromide (15.8 g). The reaction mixture was stirred at room temperature for 40 minutes and cooled to 0° C. again. Then, thereto were added triethylamine (5.5 ml) and benzyl chloroformate (4.9 ml), and the mixture was stirred for 3.5 hours at room temperature. To the mixture was added water (200 ml), and the mixture was extracted with chloroform (100 ml). The organic layer was washed with saturated aqueous sodium chloride solution, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=5/1) to give the titled compound (5.35 g).

Workup

  1. temperaturecooled to 0° C. again
  2. stirringthe mixture was stirred for 3.5 hours at room temperature
  3. extractionthe mixture was extracted with chloroform (100 ml)
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-dc0c4a81bcfc485ea2fba4e1a96c98b2
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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