4-Methylmorpholine → HCID 67773319, compound

HRID 1808780Notes

Reaction equation

HRID 1808780 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[CH3:45][O:46][CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>CN(C=O)C>[CH3:45][O:46][CH:47]1[CH2:52][CH2:51][N:50]([C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])[CH2:49][CH2:48]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 776664-MethoxypiperidineHCID 83693Boc-L-ValineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 67773319HCID 67773319, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-(Tert-butoxycarbonylamino)-3-methylbutanoic acid (2.0 g, 9.21 mmol) and TBTU (2.96 g, 9.21 mmol) were mixed in DMF (20 mL). The mixture was cooled to 0° C. and NMM (1.518 mL, 13.81 mmol) was dropwise added. After stirring for 10 min was 4-methoxypiperidine (1.272 g, 11.05 mmol) added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM (50 mL). The organic layer was washed with HCl (1M aq. solution, 100 mL), NaHCO3 (saturated, 2×100 mL) and brine (100 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified via Biotage (isocratic; DCM/MeOH, 95:5, KP-SIL 100 g column). The solvent was removed under reduced pressure to give the title compound (1.75 g, 60%). 1H NMR (400 MHz, CD3OD) δ 0.69-1.09, 1.24-1.71, 1.72-2.10, 3.09-3.27, 3.36, 3.39-3.60, 3.60-4.15, 4.20-4.49. Total no of protons: 30.

Workup

  1. additionadded
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue dissolved in DCM (50 mL)
  4. washThe organic layer was washed with HCl (1M aq. solution, 100 mL), NaHCO3 (saturated, 2×100 mL) and brine (100 mL)
  5. filtrationfiltered through a phase separator
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified via Biotage (isocratic; DCM/MeOH, 95:5, KP-SIL 100 g column)
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-abf9ff0f91fa4a3da72a82c52859d929
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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