4-Methylmorpholine → Tert-butyl (2S,3S)-1-(3-hydroxyazetidin-1-yl)-3-methyl-1-oxopentan-2-ylcarbamate

HRID 1808800Notes

Reaction equation

HRID 1808800 reaction equation
C[N:2]1[CH2:7][CH2:6][O:5]C[CH2:3]1.[C:8]([O:12][C:13]([NH:15][C@@H:16]([C@@H:20]([CH3:23])[CH2:21][CH3:22])[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.N1CC(O)C1>CN(C=O)C.C(Cl)Cl>[OH:5][CH:6]1[CH2:7][N:2]([C:17](=[O:19])[C@@H:16]([NH:15][C:13](=[O:14])[O:12][C:8]([CH3:9])([CH3:10])[CH3:11])[C@@H:20]([CH3:23])[CH2:21][CH3:22])[CH2:3]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2724762tert-Butoxycarbonyl-L-isoleucineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27592903-Hydroxyazetidine hydrochloride

Product 1

HCID 69872277Tert-butyl (2S,3S)-1-(3-hydroxyazetidin-1-yl)-3-methyl-1-oxopentan-2-ylcarbamateYield 97.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

NMM (6.12 mL, 55.6 mmol) in DMF (5 mL) was added to (2S,3S)-2-(tert-butoxycarbonylamino)-3-methylpentanoic acid (4.15 g, 17.9 mmol), which is commercially available, in DCM (45 mL) under a nitrogen atmosphere. TBTU was added portionwise and the resultant mixture was stirred at rt for 15 min. Azetidin-3-ol hydrochloride (2.359 g, 21.53 mmol) was added and the stirring continued for 20 h. The mixture was diluted with DCM, washed with NaHCO3 and brine, filtered through a phase separator and concentrated under reduced pressure. The residue was dissolved in Et2O, washed with water, filtered through a phase separator and concentrated under reduced pressure to give the title compound (5 g, 97%). The obtained crude product was used without further purification. 1H NMR (600 MHz, CDCl3) δ 0.81-0.95, 1.04-1.16, 1.35-1.48, 1.48-1.70, 3.79-4.09, 4.14-4.24, 4.25-4.42, 4.52-4.74, 5.05-5.16.

Workup

  1. washwashed with NaHCO3 and brine
  2. filtrationfiltered through a phase separator
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in Et2O
  5. washwashed with water
  6. filtrationfiltered through a phase separator
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bacd4706de9141f6b4b977afb1896193
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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