Diisopropylethylamine → HCID 89690304, compound

HRID 714034Notes

Reaction equation

HRID 714034 reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH2:11]([O:18][C:19]1[C:20]([C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)=[CH:21][C:22]([CH2:40][CH3:41])=[C:23]([CH:39]=1)[O:24][CH2:25][CH2:26][CH2:27][O:28][C:29]1[C:30]([CH2:36][CH2:37][CH3:38])=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH2:32])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:49][C:50]1([CH3:57])[CH2:54][C:53](=[O:55])[O:52][C:51]1=[O:56]>C1COCC1>[CH2:11]([O:18][C:19]1[C:20]([C:42]2[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=2)=[CH:21][C:22]([CH2:40][CH3:41])=[C:23]([CH:39]=1)[O:24][CH2:25][CH2:26][CH2:27][O:28][C:29]1[C:30]([CH2:36][CH2:37][CH3:38])=[C:31]([NH:32][C:53](=[O:55])[CH2:54][C:50]([CH3:57])([CH3:49])[C:51]([OH:56])=[O:52])[CH:33]=[CH:34][CH:35]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 870672,2-Dimethylsuccinic anhydrideHCID 89690170HCID 89690170, compound

Product 1

HCID 89690304HCID 89690304, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Add diisopropylethylamine (57 mL, 327 mmol) to a suspension of 3-[3-[5-benzyloxy-2-ethyl-4-(4-fluorophenyl)phenoxy]propoxy]-2-propyl-aniline hydrochloride (90 g, 175 mmol) in THF (450 mL). To this mixture, add dihydro-3,3-dimethyl-2,5-furandione (32.1 g, 251 mmol) and stir at 35° C. until LCMS indicates 5% starting material remaining. Concentrate the mixture in vacuo and add methyl tert-butyl ether (100 mL) and water (75 mL). Adjust to pH=2-3 with phosphoric acid and separate the layers. Wash the aqueous layer with additional methyl tert-butyl ether (2×50 mL). Wash the combined organic extracts with brine and concentrate in vacuo. Dissolve the crude residue in methyl tert-butyl ether (180 mL) and add hexane (450 mL) to obtain a suspension and stir for 30 min. Collect the suspension by filtration and dry to yield the title compound (92.5 g, 88%) as a white solid. ES/MS m/z 642 (M+1).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd methyl tert-butyl ether (100 mL) and water (75 mL)
  3. customseparate the layers
  4. washWash the aqueous layer with additional methyl tert-butyl ether (2×50 mL)
  5. washWash the combined organic extracts with brine
  6. concentrationconcentrate in vacuo
  7. dissolutionDissolve the crude residue in methyl tert-butyl ether (180 mL)
  8. additionadd hexane (450 mL)
  9. customto obtain a suspension
  10. stirringstir for 30 min
  11. customCollect the suspension
  12. filtrationby filtration
  13. customdry

Sources & evidence

ORD record
ord-983e27bf243c492091c89f5bdad66cec
Source dataset
uspto-grants-2015_11
Patent number
US09187411B2

Reaction notes

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