Triethylamine → 1-(2,8-Dimethyl-1-oxa-3,8-diaza-spiro[4.5]dec-3-yl)-2-propyl-pentan-1-one

HRID 574627Notes

Reaction equation

HRID 574627 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)[O:3]1.C(N(CC)CC)C.[C:20](Cl)(=[O:28])[CH:21]([CH2:25][CH2:26][CH3:27])[CH2:22][CH2:23][CH3:24]>ClCCl>[CH3:1][CH:2]1[N:6]([C:20](=[O:28])[CH:21]([CH2:25][CH2:26][CH3:27])[CH2:22][CH2:23][CH3:24])[CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[O:3]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 762402-Propylvaleryl chlorideHCID 197553342,8-Dimethyl-1-oxa-3,8-diazaspiro[4.5]decane

Product 1

HCID 468468111-(2,8-Dimethyl-1-oxa-3,8-diaza-spiro[4.5]dec-3-yl)-2-propyl-pentan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2,8-Dimethyl-1-oxa-3,8-diaza-spiro[4.5]decane (1.52 g, 8.95 mmol) was dissolved in dry dichloromethane (5 ml) under an argon atmosphere. Distilled triethylamine (1.87 ml, 13.42 mmol) was added and the resulting solution was cooled to 0° C. Valproyl chloride (1.46 g, 8.95 mmol) was added dropwise with a syringe. The reaction flask was allowed to warm to room temperature with stirring, and a white solid started to precipitate. After 4 h of stirring, dichloromethane (100 ml) was added and the resulting solution was washed with water (10 ml). The two phases were separated and the aqueous phase was extracted with dichloromethane (2×50 ml). The combined organic phase was dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 130/10/1) to give AF712 (389 mg, 98.7% chemical purity) as a yellow powder. 1H NMR (CDCl3, 300 MHz) δ 5.43 (q, J=5.2 Hz, 1H, CHCH3), 4.13, 3.63 (2d, J=11.35 and J=9.6 Hz, 1H, CHHNCO), 3.22, 3.00 (2d, J=9.6 and J=11.35 Hz, 1H, CHHNCO), 2.56-2.38 (m, 5H), 2.30, 2.29 (2s, 3H, NCH3), 1.84-1.53 (3m, 6H), 1.44, 1.43 (2d, J=5.2 Hz, 3H, CH3CH), 1.4-1.19 (m, 6H), 0.90 (app t, J=7.11 Hz, 6H, CH3CH2) ppm; 13C NMR (CDCl3, 300 MHz) δ 173.92, 173.68 (C), 84.75, 84.20 (CH), 78.32, 78.09 (C), 54.24 (CH2), 52.34 (CH2), 52.02 (CH2), 46.03 (CH3), 44.34, 43.64 (CH), 35.63 (CH2), 35.05 (CH2), 34.92 (CH2), 32.83 (CH2), 23.52, 20.91 (CH3), 20.59 (CH2), 20.43 (CH2), 14.30 (CH3), 14.16 (CH3) ppm.

Workup

  1. temperatureto warm to room temperature
  2. customto precipitate
  3. stirringAfter 4 h of stirring
  4. additiondichloromethane (100 ml) was added
  5. washthe resulting solution was washed with water (10 ml)
  6. customThe two phases were separated
  7. extractionthe aqueous phase was extracted with dichloromethane (2×50 ml)
  8. dry with materialThe combined organic phase was dried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe residue was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 130/10/1)
  12. customto give AF712 (389 mg, 98.7% chemical purity) as a yellow powder

Sources & evidence

ORD record
ord-0267056d619d448f93346f43d30ebe12
Source dataset
uspto-grants-2015_05
Patent number
US09034891B2

Reaction notes

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