Diisopropylethylamine → HCID 67773077, compound

HRID 1808804Notes

Reaction equation

HRID 1808804 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([OH:6])[CH2:3]1.[CH:7]1([CH:12]([NH:16][C:17]([O:19][CH3:20])=[O:18])[C:13](O)=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8]1.CCN(C(C)C)C(C)C.OS([O-])(=O)=O.[K+]>C(Cl)Cl.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>[CH:7]1([CH:12]([NH:16][C:17](=[O:18])[O:19][CH3:20])[C:13]([N:2]2[CH2:5][CH:4]([OH:6])[CH2:3]2)=[O:14])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 27592903-Hydroxyazetidine hydrochloride2×HCID 67167194HCID 67167194, compound

Product 1

HCID 67773077HCID 67773077, compoundYield 155.7%

Reagents, catalysts & solvents 2

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

TBTU (0.373 g, 1.16 mmol) was added to azetidin-3-ol hydrochloride (1.960 g, 17.89 mmol), 2-cyclopentyl-2-(methoxycarbonylamino)acetic acid (Compound J2.1) (3 g, 14.91 mmol) and DIPEA (10 mL, 57.3 mmol) in DCM (60 mL) at rt. The resultant mixture was stirred for 2 h. Additional azetidin-3-ol hydrochloride (0.45 g, 4.11 mmol) was added and the mixture was heated at 50° C. for 1.5 h. The mixture was cooled to rt and the pH was adjusted to 2 using KHSO4 (1.5 M). The mixture was extracted with DCM and the combined DCM layers were washed with brine and concentrated under reduced pressure. The residue was diluted with MeOH (15 mL) and KOH (1.56 g) in water (30 mL) was added. The resultant mixture was stirred at rt for 5 h. Part of the solvent was removed under reduce pressure. The remaining mixture was diluted with water and extracted with DCM. The organic layer was washed with brine, dried (MgSO4) and concentrated under reduce pressure. The residue was purified via Biotage (gradient: 10-100% of DCM/MeOH (1:0.05) in DCM, KP-SIL 100 g column) to give the title product (5.95 g, 50%). 1H NMR (600 MHz, CDCl3) 1.15-1.40, 1.45-1.81, 2.04-2.20, 2.33, 2.50, 3.65, 3.84, 3.92, 4.04, 4.14-4.28, 4.32, 4.37-4.44, 4.65, 5.25. Total no of protons: 20.

Workup

  1. temperatureThe mixture was cooled to rt
  2. extractionThe mixture was extracted with DCM
  3. washthe combined DCM layers were washed with brine
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with MeOH (15 mL) and KOH (1.56 g) in water (30 mL)
  6. additionwas added
  7. customPart of the solvent was removed
  8. additionThe remaining mixture was diluted with water
  9. extractionextracted with DCM
  10. washThe organic layer was washed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe residue was purified via Biotage (gradient: 10-100% of DCM/MeOH (1:0.05) in DCM, KP-SIL 100 g column)

Sources & evidence

ORD record
ord-0aec9c86a7dc45a1a0a12c17309bc97b
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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