4-Methylmorpholine → HCID 54390047, compound

HRID 990344Notes

Reaction equation

HRID 990344 reaction equation
[CH3:1][CH:2]([CH3:15])[CH2:3][C@H:4]([NH:8][CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:5]([OH:7])=O.CN1CCOCC1.Cl.[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[CH2:32][CH2:33][CH2:34][NH2:35])=[CH:27][CH:26]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CO>[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)[CH2:32][CH2:33][CH2:34][NH:35][C:5](=[O:7])[C@@H:4]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH2:3][CH:2]([CH3:1])[CH3:15])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15458709HCID 15458709, compoundHCID 18418679HCID 18418679, compound

Product 1

HCID 54390047HCID 54390047, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of (S)-4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoic acid (430 mg, 2.00 mmol), N-methylmorpholine (0.220 mL, 2.00 mmol), and 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (597 mg, 2.00 mmol) in dry DMF (10 mL) was treated with Triton® B (1.82 mL, 4.00 mmol, 40 weight percent solution in methanol, Aldrich, Milwaukee, Wis.), a clear solution was obtained and cooled to 0° C. in an ice-water bath. Solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.760 g, 2.00 mmol) was then added. After stirring at 0° C. for 30 minutes, was added, the cooling bath was then removed, and the stirring was continued at ambient temperature for 30 minutes. After this period, the reaction mixture was mixed with 50 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was purified by flash chromatography (EtOAc:hexanes:MeOH 50:50:5) to give 300 mg (39%) of the pure titled compound as a clear oil. APCI-MS m/z 459.4 (MH+).

Workup

  1. customa clear solution was obtained
  2. additionwas added
  3. customthe cooling bath was then removed
  4. waitthe stirring was continued at ambient temperature for 30 minutes
  5. waitAfter this period
  6. additionthe reaction mixture was mixed with 50 mL of diethyl ether
  7. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL)
  8. dry with materialwas dried over Na2SO4
  9. concentrationThe solution was concentrated in vacuo
  10. customaffording a viscous oil
  11. customThe crude product was purified by flash chromatography (EtOAc:hexanes:MeOH 50:50:5)

Sources & evidence

ORD record
ord-ffd8a3b3e9a84416854501c80afaadcf
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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