Hydrochloric Acid → 10-Ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane

HRID 72902Notes

Reaction equation

HRID 72902 reaction equation
[CH2:1]([CH:3]1[O:20][C:7]2([CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]2)[CH2:6][N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:4]1)[CH3:2].Cl.O1CCOCC1>ClCCl.C(=O)(O)[O-].[Na+]>[CH2:1]([CH:3]1[O:20][C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 70872778Tert-butyl 10-ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 6831112210-Ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecaneYield 99.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Tert-butyl 10-ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (480 mg, 1.33 mmol) was dissolved in dichloromethane (5 mL) at 0° C. and treated dropwise with HCl in dioxane (2.65 mL of 4 M, 10.6 mmol). The reaction was then allowed to warm to room temperature and stirred for 1 h. The reaction mixture was diluted with dichloromethane (50 mL) and saturated sodium bicarbonate solution. The organic layer was separated and the aqueous layer extracted with dichloromethane (3×20 mL). The aqueous layer was further diluted with 25 mL of 1 N NaOH and extracted with dichloromethane (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to provide 10-ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane (345 mg, 1.32 mmol, 99%) an orange-colored oil. ESI-MS m/z calc. 261.2. Found 262.3 (M+1)+; Retention time: 0.3 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 8.08 (dd, J=4.9, 1.4 Hz, 1H), 7.50 (ddd, J=8.8, 7.1, 2.0 Hz, 1H), 6.84 (d, J=8.6 Hz, 1H), 6.60 (dd, J=6.6, 5.0 Hz, 1H), 4.17 (t, J=11.3 Hz, 2H), 3.58-3.54 (m, 2H), 2.96-2.84 (m, 1H), 2.81-2.71 (m, 1H), 2.71-2.65 (m, 2H), 2.55 (d, J=12.9 Hz, 1H), 2.40 (dd, J=12.6, 11.0 Hz, 1H), 1.93 (d, J=13.9 Hz, 1H), 1.59-1.38 (m, 5H), 0.96 (t, J=7.5 Hz, 3H).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer extracted with dichloromethane (3×20 mL)
  3. additionThe aqueous layer was further diluted with 25 mL of 1 N NaOH
  4. extractionextracted with dichloromethane (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9aac13e68b034954bffd6721ee60381e
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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