Morpholine → 1-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-morpholinoethane-1,2-dione

HRID 577871Notes

Reaction equation

HRID 577871 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36][C@H:35]([CH3:40])[CH2:34]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([OH:29])=O)[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1.C(N(CC)CC)C>CN(C=O)C.O>[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:33]2[CH2:34][C@H:35]([CH3:40])[O:36][C@H:37]([CH3:39])[CH2:38]2)=[C:22]([F:32])[C:23]([F:31])=[C:24]([C:26](=[O:30])[C:27]([N:65]2[CH2:70][CH2:69][O:68][CH2:67][CH2:66]2)=[O:29])[CH:25]=1)([C:14]([CH3:15])([CH3:17])[CH3:16])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866580682-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid2×

Product 1

HCID 866580691-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-morpholinoethane-1,2-dioneYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid (Intermediate 118, 150 mg, 0.26 mmol), HATU (121 mg, 0.32 mmol), morpholine (0.025 ml, 0.29 mmol) and triethylamine (0.055 ml, 0.40 mmol) in DMF (5 ml) were stirred at room temperature for 1 hour. The reaction was diluted with water and extracted twice with ethyl acetate. The organic layers were washed three times with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate to give the title compound (130 mg, 0.204 mmol, 77%)

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe organic layers were washed three times with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give an oil
  6. customThe oil was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3a601c93b25943c48554167b6dea6301
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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