Ethyl Acetate → HCID 70332669, compound

HRID 2235833Notes

Reaction equation

HRID 2235833 reaction equation
[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]

Participants

9

Reactant 4

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

Product 1

HCID 70332669HCID 70332669, compoundYield 61.4%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-59ba03062683404b8cf4e985fca09711
Source dataset
uspto-grants-2010_05
Patent number
US07714023B2

Reaction notes

Loading…