Morpholine → HCID 57736985, compound

HRID 1971131Notes

Reaction equation

HRID 1971131 reaction equation
C(OC([NH:11][C@@H:12]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]([OH:15])=O)=O)C1C=CC=CC=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.[Pd]>[NH2:11][C@@H:12]([C:16]([CH3:17])([CH3:18])[CH3:19])[C:13]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:15]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 9899995(2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acid

Product 1

HCID 57736985HCID 57736985, compoundYield 96.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-(benzyloxycarbonylamino)-3,3-dimethylbutanoic acid (2.0 g, 7.54 mmol) in DMF (10 mL) were added morpholine (1.31 g, 15.1 mmol) and DIEA (3.95 mL, 22.62 mmol). TBTU (3.63 g, 11.31 mmol) was added in three portions 15 minutes apart. The reaction stirred at room temperature for 2 hours. DMF was removed under vacuum and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude material (2.11 g, 7.54 mmol) was combined with palladium on carbon, 10% dry basis, (0.29 g, 2.69 mmol) in MeOH (15 mL) and placed on a Parr Shaker under H2 atmosphere, 20 psi, for 3 hours. The reaction was filtered through a celite plug and concentrated under reduced pressure to provide 1.46 g (7.31 mmol) of intermediate 77D. LCMS (+ESI) m/z 201.1 [M+H]+.

Workup

  1. customDMF was removed under vacuum
  2. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dry with materialdry basis, (0.29 g, 2.69 mmol) in MeOH (15 mL)
  8. wait20 psi, for 3 hours
  9. filtrationThe reaction was filtered through a celite plug
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-56e7052a65e8413dae402a7f6fdbcda5
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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