Diisopropylethylamine → HCID 178451982, compound

HRID 1480428Notes

Reaction equation

HRID 1480428 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([OH:11])=O)[O:4][N:3]=1.CCN(C(C)C)C(C)C.[C:21]([N:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH2:35])[CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CN(C=O)C>[OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([NH:35][CH2:34][CH:31]2[CH2:32][CH2:33][N:28]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:29][CH2:30]2)=[O:11])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 1785253353-(3-Hydroxy-5-isoxazolyl)propanoic acid

Product 1

HCID 178451982HCID 178451982, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3-(3-hydroxyisoxazol-5-yl)propanoic acid (300 mg, 1.909 mmol) in DMF (7 mL) was added DIPEA (0.667 mL, 3.82 mmol) followed by 1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholino)]uronium hexafluorophosphate (COMU) (981 mg, 2.291 mmol). The resulting brown solution was stirred at RT for 5 mins and then treated with 1-BOC-4-(aminomethyl)piperidine (409 mg, 1.909 mmol). After stirring at RT for 2 hrs, the solution was concentrated under reduced pressure and the residue suspended in 0.2M aqueous HCl (200 ml). The mixture was extracted with EtOAc (2×100 ml) and the combined extracts were dried (MgSO4) and concentrated under reduced pressure. The crude residue was dissolved in DCM (100 ml) and treated with 2M NaOH (50 ml). The mixture was stirred vigorously at ambient temperature for 16 hrs. The mixture was then acidified with citric acid and the organics removed, dried (MgSO4) and concentrated under reduced pressure. The residue was applied to a 24 g silica cartridge and eluted with 0-100% EtOAc/iso-hexane. The product fractions were combined and concentrated to give a tert-butyl 4-((3-(3-hydroxyisoxazol-5-yl)propanamido)methyl)piperidine-1-carboxylate as a gum.

Workup

  1. stirringAfter stirring at RT for 2 hrs
  2. concentrationthe solution was concentrated under reduced pressure
  3. extractionThe mixture was extracted with EtOAc (2×100 ml)
  4. dry with materialthe combined extracts were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude residue was dissolved in DCM (100 ml)
  7. additiontreated with 2M NaOH (50 ml)
  8. stirringThe mixture was stirred vigorously at ambient temperature for 16 hrs
  9. dry with materialthe organics removed, dried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. washeluted with 0-100% EtOAc/iso-hexane
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-14a55c83fe7e43fdafb391331f234936
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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