2-Methoxyethanol → 2-Chloro-3-fluoro-5-(2-methoxyethoxy)pyridine

HRID 221793

反応式

HRID 221793 の反応式
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[CH3:10][O:11][CH2:12][CH2:13]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.[Cl-].[Na+].O.CCOC(C)=O.O>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([O:8][CH2:13][CH2:12][O:11][CH3:10])=[CH:6][N:7]=1

参加物

9

反応物 4

HCID 80192-MethoxyethanolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 404247372-Chloro-3-fluoro-5-hydroxypyridine

生成物 1

HCID 866502752-Chloro-3-fluoro-5-(2-methoxyethoxy)pyridine

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of 6-chloro-5-fluoro-pyridin-3-ol (CAS registry 870062-76-3) (800 mg, 5.42 mmol), 2-methoxy-ethanol (454 mg, 0.471 ml, 5.96 mmol) and triphenylphosphine (2.199 g, 8.13 mmol) in THF (40 ml) was added dropwise a solution of DIAD (1.731 g, 8.13 mmol) in THF (20 ml) while keeping the temperature at 0-5° C. The reaction mixture was stirred for 20 h at room temperature, water and brine were added and the mixture was diluted with EtOAc. The aqueous layer was twice extracted with EtOAc, the combined organic layers were dried over Na2SO4, filtered, the filtrate was concentrated and yielded after trituration with Et2O and filtration, the title compound as a white solid. The filtrate yielded another batch of the product after purification by prep. NP HPLC using an Alltech Grom Saphir 65 Si 10 μM 250×50 mm column (heptane/EtOAc, gradient 0-1.7 min 15% EtOAc, 1.7-17 min 15-100% EtOAc, 17-24.3 min 100% EtOAc, 24.3-27.8 min 0% EtOAc).

後処理

  1. customat 0-5° C
  2. extractionThe aqueous layer was twice extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customyielded after trituration
  7. filtrationwith Et2O and filtration
  8. customThe filtrate yielded another batch of the product
  9. customafter purification by prep
  10. customan Alltech Grom Saphir 65 Si 10 μM 250×50 mm column (heptane/EtOAc, gradient 0-1.7 min 15% EtOAc, 1.7-17 min 15-100% EtOAc, 17-24.3 min 100% EtOAc, 24.3-27.8 min 0% EtOAc)

出典と根拠

ORDレコード
ord-2000072fbf1840979c95f983ad530b72
出典データセット
uspto-grants-2012_06
特許番号
US08207164B2

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