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

HRID 1912383Notes

Reaction equation

HRID 1912383 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].C(=O)(O)[O-].[Na+]>ClCCl.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 5

HCID 10387Benzyl chloroformateHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 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 2

HCID 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 (12.9 g), triphenylphosphine (20.3 g) and triethylamine (21.6 ml) in dichloromethane (400 ml) cooled to 0° C. was added carbon tetrabromide (25.9 g) in small batches. The reaction mixture was stirred at room temperature for 1 hour, and the mixture was cooled to 4° C. Then, thereto were added triethylamine (10.8 ml) and benzyl chloroformate (10.3 ml), and the mixture was stirred at room temperature for 40 minutes. To the mixture was added 5% aqueous sodium bicarbonate solution (125 ml), and the mixture was extracted with chloroform (125 ml). The separated aqueous layer was extracted with chloroform (125 ml) again. The combined organic layer was washed with water (125 ml), 10% aqueous sodium chloride solution (125 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 7/3) to give the titled compound (12.4 g).

Workup

  1. temperaturethe mixture was cooled to 4° C
  2. stirringthe mixture was stirred at room temperature for 40 minutes
  3. extractionthe mixture was extracted with chloroform (125 ml)
  4. extractionThe separated aqueous layer was extracted with chloroform (125 ml) again
  5. washThe combined organic layer was washed with water (125 ml), 10% aqueous sodium chloride solution (125 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 7/3)

Sources & evidence

ORD record
ord-f3a41ff6ba634c28992661d7e8a48a65
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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