Ethyl Acetate → HCID 70332669、化合物

HRID 2235833ノート

反応式

HRID 2235833 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:19][CH2:20][CH:21]=O)[C:16]3[C:11](=[CH:12][C:13]([C:17]#[N:18])=[CH:14][CH:15]=3)[CH2:10][O:9]2)=[CH:4][CH:3]=1.[C:23]([S:27]([NH2:29])=[O:28])([CH3:26])([CH3:25])[CH3:24].CCOC(C)=O.[BH4-].[Na+]>C1COCC1.CCO.[Cl-].[Na+].O.CCCCCC>[C:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[C:8]([CH2:19][CH2:20][CH2:21][NH:29][S:27]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:28])([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[O:9][CH2:10]2)#[N:18]

参加物

9

反応物 4

HCID 8857Ethyl Acetate2 回HCID 3382465Tert-ButanesulfinamideHCID 4311764Sodium borohydrideHCID 9944000Citalopram aldehyde

生成物 1

HCID 70332669HCID 70332669、化合物収率 61.4%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

1-(4-fluorophenyl)-1-(3-oxopropyl)-1,3-dihydro-isobenzofuran-5-carbonitrile (3.0 g) was dissolved in THF (20 mL), followed by addition of (−)-tert-butylsulfinamide (1.5 g), and Ti (OEt)4 (20 mL, Aldrich) in EtOH. The reaction mixture was stirred at room temperature for 10 min, and 55° C. for 1 h. The reaction mixture was cooled to 5-10° C., was added brine (50 mL), and EtOAc (150 mL). The reaction mixture was stirred at room temperature for 10 min and filtered. The EtOAc layer in the filtrate was separated and washed with brine and concentrated to give a crude oil. It was dissolved in THF (20 ml), cooled to 5-10° C. and added NaBH4 (1.6 g) Methanol (10 mL). The reaction mixture was stirred for 14 h, quenched with water at 5-10° C., extracted with EtOAc (100 mL). The extract was washed with brine and concentrated to give the crude product (3.5 g). It was passed through a silica gel column using EtOAc and hexane (8:2) to give the pure product (2.5 g) as a mixture of possible diastereomers. 1H NMR (CDCl3, δ): 1.19 (s, 9H), 1.40-1.60 (m, 2H), 2.10-2.30 (m, 2H), 3.05-3.30 (m, 3H), 5.17 (m, 2H). 7.00 (m, 2H), 7.40-7.60 (m, 5H). 13C NMR(CDCl3, δ): 22.4, 25.6, 38.1, 45.4, 55.4, 71.1, 90.7, 111.6, 115.1, 115.4, 118.4, 122.6, 125.1, 126.5, 126.6, 131.8, 139.1, 140.1, 149.0, 160.2, 163.5.

後処理

  1. wait55° C. for 1 h
  2. temperatureThe reaction mixture was cooled to 5-10° C.
  3. stirringThe reaction mixture was stirred at room temperature for 10 min
  4. filtrationfiltered
  5. customThe EtOAc layer in the filtrate was separated
  6. washwashed with brine
  7. concentrationconcentrated
  8. customto give a crude oil
  9. temperaturecooled to 5-10° C.
  10. stirringThe reaction mixture was stirred for 14 h
  11. customquenched with water at 5-10° C.
  12. extractionextracted with EtOAc (100 mL)
  13. washThe extract was washed with brine
  14. concentrationconcentrated
  15. customto give the crude product (3.5 g)

出典と根拠

ORDレコード
ord-59ba03062683404b8cf4e985fca09711
出典データセット
uspto-grants-2010_05
特許番号
US07714023B2

反応ノート

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