Ethyl 1-(aminomethyl)spiro[2.5]octane-1-carboxylate → 1-(aminomethyl)spiro[2.5]octane-1-carboxylic Acid

HRID 1796816Notes

Reaction equation

HRID 1796816 reaction equation
C([O:3][C:4]([C:6]1([CH2:14][NH2:15])[C:8]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH2:7]1)=[O:5])C>Cl>[NH2:15][CH2:14][C:6]1([C:4]([OH:5])=[O:3])[C:8]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH2:7]1

Participants

3

Reactant 1

HCID 69599863Ethyl 1-(aminomethyl)spiro[2.5]octane-1-carboxylate

Product 1

HCID 101038441-(aminomethyl)spiro[2.5]octane-1-carboxylic AcidYield 3.9%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To 1-aminomethyl-spiro[2.5]octane-1-carboxylic acid ethyl ester (5.0 g, 23.7 mmol) was added 50 mL 3N HCl (aq), and the mixture was refluxed for 72 hours. The crude 1H NMR indicated the hydrolysis had proceeded to 50% completion. The solution was concentrated, and the residue washed exhaustively with Et2O to remove the starting material, until a fine white solid was obtained. The combined solids were washed again with Et2O (3×15 mL) to give a chalky solid. A small portion of the batch was recrystallized from MeOH/EtOAc to furnish 0.17 g (3.3%) of 1-aminomethyl-spiro[2.5]octane-1-carboxylic acid as a colorless solid, mp>250° C. (dec): 1H NMR (D2O) δ 3.37 (d, J=13.4 Hz, 1H), 2.83 (d, J=13.4 Hz, 1H), 1.21–1.33 (m, 10H), 0.99 (d, J=5.1 Hz, 1H), 0.47 (d, J=5.1 Hz, 1H). Anal. Calcd for C10H17NO2.HCl: C, 54.67; H, 8.26; N, 6.37. Found: C, 54.77; H, 8.41; N, 6.31. A second crop was also obtained (0.34 g, 6.6%). Anal. Calcd for C10H17NO2.HCl: C, 54.67; H, 8.26; N, 6.37. Found: C, 54.71; H, 8.42; N, 6.22. The Et2O washings were concentrated to provide 1-aminomethyl-spiro[2.5]octane-1-carboxylic acid ethyl ester hydrochloride as a colorless solid, mp 118–120° C.: 1H NMR (CDCl3) δ 8.39 (br s, 3H), 4.23 (m, 2H), 3.66 (m, 1H), 3.31 (m, 1H), 1.85 (m, 1H), 1.65 (m, 1H), 1.42–1.54 (m, 9H), 1.28 (t, J=7.1 Hz, 3H), 1.03 (d, J=5.4 Hz, 1H). Anal. Calcd for C12H21NO2.HCl: C, 58.17; H, 8.95; N, 5.65. Found: C, 58.31; H, 8.87; N, 5.51.

Workup

  1. temperaturethe mixture was refluxed for 72 hours
  2. concentrationThe solution was concentrated
  3. washthe residue washed exhaustively with Et2O
  4. customto remove the starting material
  5. customuntil a fine white solid was obtained
  6. washThe combined solids were washed again with Et2O (3×15 mL)
  7. customto give a chalky solid
  8. customA small portion of the batch was recrystallized from MeOH/EtOAc

Sources & evidence

ORD record
ord-6ff5266d7a7c4b4d8ce4666d05a613d3
Source dataset
uspto-grants-2006_04
Patent number
US07030267B2

Reaction notes

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