Diisopropylethylamine → HCID 86691898, compound

HRID 517785Notes

Reaction equation

HRID 517785 reaction equation
[Cl:1][CH2:2][C:3]1[N:7]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=2)[N:6]=[N:5][N:4]=1.Cl.[CH:21]12[NH:28][CH:25]([CH2:26][CH2:27]1)[CH2:24][O:23][CH2:22]2.C(N(C(C)C)CC)(C)C>C(#N)C.C(Cl)Cl.Cl.C(OCC)C>[ClH:1].[CH:25]12[N:28]([CH2:2][C:3]3[N:7]([C:8]4[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=4)[N:6]=[N:5][N:4]=3)[CH:21]([CH2:27][CH2:26]1)[CH2:22][O:23][CH2:24]2

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 534011293-Oxa-8-azabicyclo(3.2.1)octane hydrochloride2×HCID 66654576HCID 66654576, compound2×

Product 1

HCID 86691898HCID 86691898, compoundYield 60.4%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 4-[5-(chloromethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile (Intermediate 24, 1.70 g, 5.91 mmol) and 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (Intermediate 27, 0.884 g, 5.91 mmol) in acetonitrile (25 mL) was added di-isopropylethylamine (2.06 mL, 11.8 mmol). The reaction was heated to 85° C. and stirred for 6 hours. The reaction was cooled and the solvent removed under vacuum. The residue was partitioned between DCM (100 mL) and water (50 mL). The aqueous layer was separated and extracted with DCM (50 mL). The DCM layers were combined and the solvent removed. The residue was purified by silica chromatography (Biotage SP4, eluting a gradient of ethyl acetate in iso-hexane) to yield a colourless gum. The product was dissolved in a minimum of DCM before the addition of 1N HCl in diethyl ether (10 mL). The solvent was removed from the resulting suspension. The solid obtained was triturated with diethyl ether (5 mL), the ether decanted and the solid dried under vacuum at 40° C. for 18 hours to yield the title compound as a white solid (1.43 g).

Workup

  1. temperatureThe reaction was cooled
  2. customthe solvent removed under vacuum
  3. customThe residue was partitioned between DCM (100 mL) and water (50 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with DCM (50 mL)
  6. customthe solvent removed
  7. customThe residue was purified by silica chromatography (Biotage SP4
  8. washeluting a gradient of ethyl acetate in iso-hexane)
  9. customto yield a colourless gum
  10. customThe solvent was removed from the resulting suspension
  11. customThe solid obtained
  12. customwas triturated with diethyl ether (5 mL)
  13. customthe ether decanted
  14. customthe solid dried under vacuum at 40° C. for 18 hours

Sources & evidence

ORD record
ord-9fc2956737e1450882a35223d6d2b5fc
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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