Dichloromethane → HCID 14502136, compound

HRID 704182Notes

Reaction equation

HRID 704182 reaction equation
[BH4-].[Na+].[C:3]([C:5]1[CH:18]=[CH:17][C:16]2[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]([CH:19]([CH3:25])[C:20](OCC)=[O:21])[C:7]=2[CH:6]=1)#[N:4].[OH-].[Na+].C(Cl)Cl>O1CCCC1.C(S)CS>[OH:21][CH2:20][CH:19]([N:8]1[C:7]2[CH:6]=[C:5]([C:3]#[N:4])[CH:18]=[CH:17][C:16]=2[S:15][C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH3:25]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium Hydroxide2×HCID 4311764Sodium borohydrideHCID 14502135ethyl (2RS)-2-(2-cyano-10-phenothiazinyl)propionate

Product 1

HCID 14502136HCID 14502136, compoundYield 65.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 109021,2-EthanedithiolSolvent

Conditions

Temperature
20 °C

Procedure

Into a suspension of sodium borohydride (52 g) in tetrahydrofuran (1.4 liters), 1,2-ethanedithiol (113 cc) is introduced with stirring in the course of 15 minutes and at a temperature in the region of 20° C., followed, in the course of 15 minutes under the same conditions, by a solution of ethyl (2RS)-2-(2-cyano-10-phenothiazinyl)propionate (296 g) in tetrahydrofuran (1.4 liters). When the addition is complete, the reaction mixture is heated for 20 hours to a temperature in the region of 60° C. After cooling to a temperature of 5° C., 4N aqueous sodium hydroxide solution (1 liter) is introduced during 1 hour: a brisk evolution of gas is observed. The reaction mixture is then poured into a mixture of 4N aqueous sodium hydroxide solution (1 liter) and methylene chloride (3 liters) with stirring. The organic phase is isolated and the aqueous phase re-extracted with methylene chloride (1 liter). The combined organic phases are washed with saturated aqueous sodium chloride solution (2×1 liter), dried over magnesium sulphate, filtered and concentrated t dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The viscous orange oil (290 g) is purified on a column (height: 50 cm; diameter: 8.5 cm) of silica gel (0.2-0.063 mm), eluting successively with methylene chloride (3 liters), then with a mixture (97.5:2.5 by volume) (4 liters) of methylene chloride and methanol and with a mixture (95:5 by volume) (10 liters) of methylene chloride and methanol and collecting 1-liter fractions. Fractions 3 to 15 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. 10-[(2RS)-1-Hydroxy-2-propyl]-2-phenothiazinecarbonitrile (169.7 g) is thereby obtained in the form of a yellow solid, m.p. 123° C.

Workup

  1. additionis introduced
  2. additionWhen the addition
  3. temperaturethe reaction mixture is heated for 20 hours to a temperature in the region of 60° C
  4. additionis introduced during 1 hour
  5. stirringwith stirring
  6. customThe organic phase is isolated
  7. extractionthe aqueous phase re-extracted with methylene chloride (1 liter)
  8. washThe combined organic phases are washed with saturated aqueous sodium chloride solution (2×1 liter)
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated t dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  12. customThe viscous orange oil (290 g) is purified on a column (height: 50 cm; diameter: 8.5 cm) of silica gel (0.2-0.063 mm)
  13. washeluting successively with methylene chloride (3 liters)
  14. customwith a mixture (97.5:2.5 by volume) (4 liters) of methylene chloride and methanol and with a mixture (95:5 by volume) (10 liters) of methylene chloride and methanol and collecting 1-liter fractions
  15. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C

Sources & evidence

ORD record
ord-c784417a21eb4b4784faa04ccbe6d7ea
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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