4-Nitrobenzoic Acid → (S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol

HRID 16373

反応式

HRID 16373 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[NH:15][C@@H:14]([C@H:16]([OH:18])[CH3:17])[CH2:13][O:12][CH2:11]2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+](C1C=CC(C(O)=O)=CC=1)([O-])=O.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C[O-].[Na+]>O.C(OCC)(=O)C.CO.O1CCCC1>[F:9][C:6]1[CH:5]=[C:4]([C@H:10]2[NH:15][C@@H:14]([C@@H:16]([OH:18])[CH3:17])[CH2:13][O:12][CH2:11]2)[CH:3]=[C:2]([F:1])[C:7]=1[F:8]

参加物

10

反応物 5

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 10942334Sodium MethoxideHCID 67374002(R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]ethanol

生成物 1

HCID 68716490(S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol収率 52.9%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Under a nitrogen atmosphere, to a tetrahydrofuran (50 mL) solution containing (R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol (2.25 g), triphenylphosphine (4.51 g) and 4-nitrobenzoic acid (2.88 g) was dropwise added diisopropyl azodicarboxylate (3.39 mL) while cooling with ice. The resultant solution was stirred at the same temperature for 30 minutes, and then at room temperature for 2 hours. The reaction solution was diluted with water and ethyl acetate, and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was crudely purified by silica gel column chromatography (heptane/ethyl acetate 8/2→1/1), to thereby obtain a crude product (3.6 g) of 4-nitrobenzoic acid (S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethyl ester. A solution of the obtained crude product (3.53 g) in methanol (300 mL) was added sodium methoxide (4.39 mL, 28% methanol solution), and the resultant solution was stirred at room temperature for 1 hour. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned, washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/1), to thereby obtain the titled compound (1.19 g). The physical properties of the compound were as follows.

後処理

  1. temperaturewhile cooling with ice
  2. customthe organic layer was partitioned
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customSolvent was removed by distillation under reduced pressure
  6. customthe resulting residue was crudely purified by silica gel column chromatography (heptane/ethyl acetate 8/2→1/1)
  7. customto thereby obtain a crude product (3.6 g) of 4-nitrobenzoic acid (S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethyl ester
  8. customSolvent was removed by distillation under reduced pressure
  9. additionthe resultant product was diluted with ethyl acetate and water
  10. customThe organic layer was partitioned
  11. washwashed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customSolvent was removed by distillation under reduced pressure
  14. customthe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/1)

出典と根拠

ORDレコード
ord-2c3fd82969b3442389151fd8092ec402
出典データセット
uspto-grants-2010_06
特許番号
US07737141B2

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