N-Methoxy-N-methylfuran-2-carboxamide → HCID 86658071, compound

HRID 577873Notes

Reaction equation

HRID 577873 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[CH:22][CH:21]=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.[Li]C(CC)C.CON(C)[C:44]([C:46]1[O:47][CH:48]=[CH:49][CH:50]=1)=[O:45]>C1COCC1>[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[C:22]([C:44]([C:46]2[O:47][CH:48]=[CH:49][CH:50]=2)=[O:45])[CH:21]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 10820793N-Methoxy-N-methylfuran-2-carboxamideHCID 67357593(2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Product 1

HCID 86658071HCID 86658071, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a stirred solution of (2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine (Intermediate 3, 1 g, 2.02 mmol) in THF (8 mL) was added sBuLi (1.3 M in cyclohexane/hexanes, 3.1 ml, 4.03 mmol) at −70° C. under nitrogen atmosphere. After stirring for 1 h at this temperature, N-methoxy-N-methylfuran-2-carboxamide (0.939 g, 6.05 mmol) was added in 3 ml of THF. After stirring for 1½ h at −70° C., the reaction quenched with sat. ammonium chloride solution and the aqueous layer extracted by ethyl acetate (2×100 mL). The organic phases were combined, dried (Na2SO4), and concentrated. The residue purified over a silica gel flash column using a gradient of ethyl acetate in hexanes to give the title compound (0.90 g, 76%).

Workup

  1. customthe reaction quenched with sat. ammonium chloride solution
  2. extractionthe aqueous layer extracted by ethyl acetate (2×100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue purified over a silica gel flash column

Sources & evidence

ORD record
ord-0a19ab95b1924ce9bcc3734b758bd074
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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