Dimethyl Sulfoxide → HCID 9867571, compound

HRID 2414842Notes

Reaction equation

HRID 2414842 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:25][O:24][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[CH:21][O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[C:26]1([N:32]2[C:36]3([CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)[C:35](=[O:42])[NH:34][CH2:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[CH3:43]S(C)=O>>[CH3:43][C:21]1[O:22][C:23]2=[C:15]3[C:16](=[CH:17][CH:18]=[C:19]2[N:20]=1)[O:24][CH2:25][CH:13]([CH2:12][N:39]1[CH2:38][CH2:37][C:36]2([N:32]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:33][NH:34][C:35]2=[O:42])[CH2:41][CH2:40]1)[O:14]3

Participants

4

Reactant 3

HCID 679Dimethyl SulfoxideHCID 705561-Phenyl-1,3,8-triazaspiro(4.5)decan-4-oneHCID 12042830HCID 12042830, compound

Product 1

HCID 9867571HCID 9867571, compound

Conditions

Temperature
77.5 °C

Procedure

(8R)-7,8-Dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methyl-benzenesulfonate (0.79 g, 2.1 mmole) and 1-phenyl-1,3,8-triazaspiro[4.5]-decan-4-one (1.46 g, 6.3 mmole) were combined in 40 mL of DMSO under nitrogen. This solution was heated to 75-80° C. under nitrogen for 4 hours. After completion, the reaction was cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 1% methanol/methylene chloride to elute 0.62 g of the desired free amine. This was recrystallized from ethanol with the addition of 0.20 g of fumaric acid to give 0.40 g of the (S)-enantiomer of the title compound as a white solid, m. p. 240° C.

Workup

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. wash1% methanol/methylene chloride to elute 0.62 g of the desired free amine
  9. customThis was recrystallized from ethanol with the addition of 0.20 g of fumaric acid

Sources & evidence

ORD record
ord-ac3cf43237644435b1bbc57a00c810a1
Source dataset
uspto-grants-2004_11
Patent number
US06815448B2

Reaction notes

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