Benzyl chloroformate → 1-Benzyl6-tert-butyl3-methyl-1,6-diazaspiro[3.5]nonane-1,6-dicarboxylate

HRID 1912393Notes

Reaction equation

HRID 1912393 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH2:18])([CH:14]([CH3:17])[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:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]>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:18]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[CH2:15][CH:14]2[CH3:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10387Benzyl chloroformateHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 582932813-Amino-3-(2-hydroxy-1-methylethyl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 582933041-Benzyl6-tert-butyl3-methyl-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-hydroxy-1-methylethyl)piperidine-1-carboxylic acid tert-butyl ester (258 mg), triphenylphosphine (472 mg) and triethylamine (502 μl) in dichloromethane (7.7 ml) cooled to 0° C. was added carbon tetrabromide (596 mg). The reaction mixture was stirred at room temperature for 2.5 hours and cooled to 4° C. Then, thereto were added triethylamine (279 μl) and benzyl chloroformate (267 μl), and the mixture was stirred for 40 minutes. To the mixture was added water, and the mixture was extracted with ethyl acetate. The separated organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1 to 2/1) to give the titled compound (85 mg).

Workup

  1. temperaturecooled to 4° C
  2. stirringthe mixture was stirred for 40 minutes
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe separated organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1 to 2/1)

Sources & evidence

ORD record
ord-5b7d9ac376974df4aa08c69aa39d8a9a
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

Loading…