Ethyl 2-chloropropionate → ethyl (2RS)-2-(7-chloro-2-cyano-10-phenothiazinyl)propionate

HRID 704227Notes

Reaction equation

HRID 704227 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]1[CH:12]=[C:11]([C:18]#[N:19])[CH:10]=[CH:9][C:8]=1[S:7]2.Cl[CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>CN(C)C=O.C(OCC)(=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:13]1[CH:12]=[C:11]([C:18]#[N:19])[CH:10]=[CH:9][C:8]=1[S:7]2

Participants

6

Reactant 3

HCID 10807Ethyl 2-chloropropionateHCID 24758Sodium hydrideHCID 159253697-Chloro-2-phenothiazinecarbonitrile

Product 1

HCID 15925368ethyl (2RS)-2-(7-chloro-2-cyano-10-phenothiazinyl)propionate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (1.85 g; in 50% strength dispersion in vaseline) is added slowly in the course of 10 minutes to a solution of 7-chloro-2-phenothiazinecarbonitrile (10 g) in N,N-dimethylformamide (250 cc). The mixture is then brought to 120° C. and treated in the course of 30 minutes with a solution of ethyl (2RS)-2-chloropropionate (18.5 cc) in N,N-dimethylformamide (100 cc). Heating is continued for 2 hours. After cooling, the mixture is diluted in ethyl acetate (1 liter) and washed with distilled water (1.5 liters). The organic phase is dried over magnesium sulphate, treated with charcoal 3S, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. to give a residue which is purified by chromatography on a column (height: 25 cm; diameter: 4.0 cm) of silica (0.2-0.06 mm), eluting with a 90:10 (by volume) mixture (1.5 liters) of cyclohexane and ethyl acetate and collecting 100-cc fractions. Fractions 6 to 11 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) to give ethyl (2RS)-2-(7-chloro-2-cyano-10-phenothiazinyl)propionate (5.3 g) in the form of a pale yellow product of meringue-like consistency.

Workup

  1. customis then brought to 120° C.
  2. temperatureHeating
  3. temperatureAfter cooling
  4. washwashed with distilled water (1.5 liters)
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. additiontreated with charcoal 3S
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C.
  9. customto give a residue which
  10. customis purified by chromatography on a column (height: 25 cm; diameter: 4.0 cm) of silica (0.2-0.06 mm)
  11. washeluting with a 90:10 (by volume) mixture (1.5 liters) of cyclohexane and ethyl acetate
  12. customcollecting 100-cc fractions
  13. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa)

Sources & evidence

ORD record
ord-8f17c8852bca425c9154f586fd98adff
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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