Diisopropylethylamine → Tert-butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

HRID 1253685Notes

Reaction equation

HRID 1253685 reaction equation
C([N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20]2([CH2:27][CH2:26][CH:25]([C:28]([OH:30])=O)[CH2:24][CH2:23]2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].O.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[N:3]1([C:28]([CH:25]2[CH2:26][CH2:27][C:20]3([CH2:19][CH2:18][N:17]([C:15]([O:14][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:16])[CH2:22][CH2:21]3)[CH2:23][CH2:24]2)=[O:30])[CH2:4][CH2:6][CH2:9][CH2:7]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 152287053-(tert-Butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid

Product 1

HCID 67547941Tert-butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.35 g, 1.18 mmol, 1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the amine (1.1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed in each case 1× with 10% strength NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol) in order to obtain the desired product. Yield: 0.23 g (56%)

Workup

  1. additionwas finally added
  2. washthe reaction mixture was washed in each case 1× with 10% strength NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (silica; ethyl acetate/ethanol) in order

Sources & evidence

ORD record
ord-e6d4a47f4d6f45f09d418153d6b727ef
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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