Ethyl 1-aminocyclopropanecarboxylate → HCID 58724139, compound

HRID 2356220Notes

Reaction equation

HRID 2356220 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH2:9])[CH2:8][CH2:7]1)=[O:5])[CH3:2].Cl[CH2:11][CH2:12][N:13]([CH2:21][CH2:22]Cl)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17]>C(N(C(C)C)CC)(C)C.[Cl-].[Na+].O>[CH2:1]([O:3][C:4]([C:6]1([N:9]2[CH2:22][CH2:21][N:13]([C:14]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:20])[CH2:12][CH2:11]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 386204Ethyl 1-aminocyclopropanecarboxylateHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 58724139HCID 58724139, compound

Reagents, catalysts & solvents 2

HCID 81531DiisopropylethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-aminocyclopropane-1-carboxylic acid ethyl ester (440 mg, 2.6 mmol) was suspended in diisopropylethylamine (2 ml). Tert-Butyl bis(2-chloroethyl)carbamate (610 mg, 2.5 mmol, prepared according to Evans et al. J. Med. Chem. 1992, 35, 3919) was added at room temperature. The suspension was stirred at room temperature for 10 minutes before being heated to 100° C. for 18 h. The resulting biphasic mixture was cooled to room temperature. Brine was added and the mixture was extracted three times with EtOAc. Combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography (SiO2, 20% EtOAc/hexanes) to give tert-butyl 4-(1-(ethoxycarbonyl)cyclopropyl)piperazine-1-carboxylate as a colorless oil (60 mg, 8% 2 steps). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm: 0.91 (m, 2 H), 1.22 (t, J=7.2 Hz, 3 H), 1.25 (m, 2H), 1.43 (s, 9 H), 2.87 (bs, 4 H), 3.27 (bs, 4 H), 4.09 (q, J=7.2 Hz, 2 H); 13C NMR (100 MHz, CHLOROFORM-D) δ ppm 14.3, 19.0, 28.4, 45.7, 49.0, 60.2, 79.4, 154.8, 174.0; ESI-MS: m/z 299.4 (M+H)+.

Workup

  1. temperaturebefore being heated to 100° C. for 18 h
  2. temperatureThe resulting biphasic mixture was cooled to room temperature
  3. extractionthe mixture was extracted three times with EtOAc
  4. dry with materialCombined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (SiO2, 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-4eaeee16cfd9428ca4dd38135623db93
Source dataset
uspto-grants-2010_07
Patent number
US07759339B2

Reaction notes

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