Diisopropylethylamine → HCID 68000123, compound

HRID 336528Notes

Reaction equation

HRID 336528 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[OH:14][CH2:15][C:16]1[O:20][N:19]=[C:18]([C:21]([O:23]CC)=O)[CH:17]=1.C([N:29](CC)C(C)C)(C)C.[NH2:35][CH:36]1[CH2:39][C:38]2([CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40]2)[CH2:37]1>ClCCCl.O>[C:21]([C:18]1[CH:17]=[C:16]([CH2:15][O:14][C:2]([NH:35][CH:36]2[CH2:37][C:38]3([CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40]3)[CH2:39]2)=[O:3])[O:20][N:19]=1)(=[O:23])[NH2:29]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 8027233Ethyl 5-(hydroxymethyl)isoxazole-3-carboxylateHCID 56962195tert-Butyl 2-amino-6-azaspiro[3.4]octane-6-carboxylate

Product 1

HCID 68000123HCID 68000123, compoundYield 73.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 0.304 g (1.51 mmol) of 4-nitrophenyl chloroformate dissolved in 5 mL of 1,2-dichloroethane is added dropwise to a solution containing 0.284 g (1.66 mmol) of ethyl 5-hydroxymethylisoxazole-3-carboxylate and 0.39 g (3.02 mmol) of N,N-diisopropylethylamine in 10 mL of 1,2-dichloroethane, cooled to about 0° C. Stirring is continued at 0° C. for 1 hour and then at room temperature for 1 hour. 0.39 g (3.02 mmol) of N,N-diisopropylethylamine and then 0.34 g (1.51 mmol) of tert-butyl 2-amino-6-azaspiro[3.4]octane-6-carboxylate, prepared in step 6.4., are added. The reaction medium is stirred at 70° C. for 4 hours. It is allowed to cool to room temperature. Water is added to the reaction medium, the aqueous phase is separated out and extracted several times with dichloromethane, the combined organic phases are washed with aqueous sodium hydroxide solution (1N) and then with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. 0.44 g of pure product is thus obtained in the form of an orange oil, which is used without further purification in the following step.

Workup

  1. additionis added dropwise to a solution
  2. waitat room temperature for 1 hour
  3. addition, are added
  4. stirringThe reaction medium is stirred at 70° C. for 4 hours
  5. temperatureto cool to room temperature
  6. customthe aqueous phase is separated out
  7. extractionextracted several times with dichloromethane
  8. washthe combined organic phases are washed with aqueous sodium hydroxide solution (1N)
  9. dry with materialwith saturated aqueous ammonium chloride solution and dried over sodium sulfate
  10. concentrationthe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-c3524bda5e0d4f5b8b9a9cb08c4392a6
Source dataset
uspto-grants-2014_11
Patent number
US08889702B2

Reaction notes

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