Triethylamine → 1-(1,1-Dimethylethyl) 3-ethyl 3-(aminocarbonyl)-1,3-azetidinedicarboxylate

HRID 1175151Notes

Reaction equation

HRID 1175151 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:17]([OH:19])=O)[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)=[O:5])[CH3:2].CC[N:22](CC)CC.ClC(OCC(C)C)=O>C1COCC1.N>[CH2:1]([O:3][C:4]([C:6]1([C:17](=[O:19])[NH2:22])[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 574158841-(tert-Butoxycarbonyl)-3-(ethoxycarbonyl)azetidine-3-carboxylic acid

Product 1

HCID 595583791-(1,1-Dimethylethyl) 3-ethyl 3-(aminocarbonyl)-1,3-azetidinedicarboxylateYield 80.5%

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Azetidine-1,3,3-tricarboxylic acid 1-tert-butyl ester 3-ethyl ester (Example 11b; 21.5 g; 78.9 mmol) and NEt3(17.6 ml; 126 mmol) are dissolved in THF (200 ml) and cooled to 0° C. Isobutyl chloroformate (15.5 ml; 118 mmol) is added dropwise. The thick suspension is stirred for another 10 minutes at 0° C., diluted with THF (200 ml) and NH3-gas introduced for 5 minutes, stirred for 15 minutes at 0° C. followed by a second NH3-gas treatment for 5 minutes. The reaction mixture is warmed to room temperature and stirred for 30 minutes, poured on water and extracted with TBME three times. The combined organic phases are dried over Na2SO4, filtered, evaporated and purified via chromatography (SiO2; TBME ) to yield the title compound as colorless crystals (17.3 g; 80%).

Workup

  1. additionintroduced for 5 minutes
  2. stirringstirred for 15 minutes at 0° C.
  3. temperatureThe reaction mixture is warmed to room temperature
  4. stirringstirred for 30 minutes
  5. additionpoured on water
  6. extractionextracted with TBME three times
  7. dry with materialThe combined organic phases are dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. custompurified via chromatography (SiO2; TBME )

Sources & evidence

ORD record
ord-84a354140ee64a0abf8a81e8f962383c
Source dataset
uspto-grants-2010_11
Patent number
US07838674B2

Reaction notes

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