4-Methylmorpholine → Tert-butyl 1,1,1-trifluoro-3-(3-hydroxyazetidin-1-yl)-3-oxopropan-2-ylcarbamate

HRID 1808810Notes

Reaction equation

HRID 1808810 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:23]([O:27][C:28]([NH:30][CH:31]([C:35]([F:38])([F:37])[F:36])[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].C[N:40]1[CH2:45][CH2:44][O:43]C[CH2:41]1.Cl.OC1CN(O)C1>C(Cl)Cl>[F:36][C:35]([F:38])([F:37])[CH:31]([NH:30][C:28](=[O:29])[O:27][C:23]([CH3:24])([CH3:25])[CH3:26])[C:32]([N:40]1[CH2:45][CH:44]([OH:43])[CH2:41]1)=[O:34]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 534037822-{[(Tert-butoxy)carbonyl]amino}-3,3,3-trifluoropropanoic acidHCID 677745913-Hydroxyazetidinol hydrochloride

Product 1

HCID 67771996Tert-butyl 1,1,1-trifluoro-3-(3-hydroxyazetidin-1-yl)-3-oxopropan-2-ylcarbamateYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

TBTU (6.87 g, 21.4 mmol) was added to a stirred suspension of 2-(tert-butoxycarbonylamino)-3,3,3-trifluoropropanoic acid, which is commercially available, in DCM (50 mL). NMM (4.4 mL, 40 mmol) and 3-hydroxyazetidinol hydrochloride (2.48 g, 22.6 mmol) were added. The mixture was stirred at rt for 4 h. The turbid solution was diluted with DCM (70 mL) and washed with NaHCO3 solution (saturated, 1×100, 2×20 mL). After drying (Na2SO4) the solvent was evaporated under reduced pressure. The residue was stirred at rt with isohexanes (60 mL) to yield the title product (3.97 g, 97%) as a colourless powder. 1H NMR (500 MHz, DMSO-d6) δ 7.86-8.05 (1H), 5.71-5.87 (1H), 4.86-5.03 (1H), 4.27-4.54 (2H), 4.04-4.15 (1H), 3.78-3.97 (1H), 3.56-3.68 (1H), 1.38-1.4 (9H). Ratio of rotamers ˜6:4.

Workup

  1. washwashed with NaHCO3 solution (saturated, 1×100, 2×20 mL)
  2. dry with materialAfter drying (Na2SO4) the solvent
  3. customwas evaporated under reduced pressure
  4. stirringThe residue was stirred at rt with isohexanes (60 mL)

Sources & evidence

ORD record
ord-9019f15f7d474c97a22133354a3e458c
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

Loading…