Propionic Acid → 1-(2,8-Dimethyl-1-thia-3,8-diaza-spiro[4.5]dec-3-yl)-propan-1-one

HRID 574625Notes

Reaction equation

HRID 574625 reaction equation
[CH3:1][CH:2]1[NH:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1.C1(N=C=NC2CCCCC2)CCCCC1.[C:28](O)(=[O:31])[CH2:29][CH3:30]>ClCCl>[CH3:1][CH:2]1[N:6]([C:28](=[O:31])[CH2:29][CH3:30])[CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1

Participants

5

Reactant 3

HCID 1032Propionic AcidHCID 10868DicyclohexylcarbodiimideHCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

Product 1

HCID 468468051-(2,8-Dimethyl-1-thia-3,8-diaza-spiro[4.5]dec-3-yl)-propan-1-oneYield 44.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]decane (Example 1) (0.86 g, 4.62 mmol) in dichloromethane (90 ml) at room temperature was added dicyclohexylcarbodiimide (DCC) (1.28 g, 6.2 mmol) followed by addition of propionic acid (0.41 ml, 5.5 mmol). The resulting solution was stirred at room temperature overnight. During the reaction a white solid precipitated. After filtration the solvent was evaporated and the crude product was purified by flash chromatography (silica, CH2Cl2/MeOH/NH4OH 90/10/1) to give the title compound (0.5 g) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 5.51, 5.19 (2q, J=6.15 and J=6.22 Hz, 1H, CHCH3), 4.63, 3.74 (2d, J=11.88 and J=11.57 Hz, 1H, CHHNCO), 3.44, 3.08 (2d, J=11.55 and J=12.09 Hz, 1H, CHHNCO), 2.8-2.6 (m, 2H), 2.5-2.2 (m, 7H, CH2, CH2CH3, NCH3), 2.2-2.0 (m, 1H), 2.0-1.8 (m, 3H) 1.52, 1.48 (2d, J=6.30 and J=6.18 Hz, 3H, CH3—CH), 1.19-1.12 (m, 3H, CH3) ppm; 13C NMR (CDCl3, 300 MHz) δ 171.6 (C), 57.5, 57.2 (CH), 55.5 (C), 54.7, 54.3 (CH2), 53.2, 53.0 (CH2), 46.3 (CH3), 38.4, 37.7 (CH2), 37.0, 36.4 (CH2), 28.8, 26.8 (CH2), 25.6, 23.6 (CH3), 9.6, 9.4 (CH3) ppm.

Workup

  1. customDuring the reaction a white solid
  2. customprecipitated
  3. filtrationAfter filtration the solvent
  4. customwas evaporated
  5. customthe crude product was purified by flash chromatography (silica, CH2Cl2/MeOH/NH4OH 90/10/1)

Sources & evidence

ORD record
ord-7784dd8a4e204aafb18b04ab26a613b3
Source dataset
uspto-grants-2015_05
Patent number
US09034891B2

Reaction notes

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