Formaldehyde → Ethyl 9-(2,3-Dichlorophenyl)-4,7-dimethyl-1,1-dioxo-2,3,4,5,6,9-hexahydropyrido-[2.3-f][1.41thiazepine-8-carboxylate

HRID 1461476Notes

Reaction equation

HRID 1461476 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[C:19]2[S:18](=[O:21])(=[O:20])[CH2:17][CH2:16][NH:15][CH2:14][C:13]=2[NH:12][C:11]([CH3:22])=[C:10]1[C:23]([O:25][CH2:26][CH3:27])=[O:24].C=O.[C:30]([BH3-])#N.[Na+].O>C(#N)C.CC(O)=O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[C:19]2[S:18](=[O:20])(=[O:21])[CH2:17][CH2:16][N:15]([CH3:30])[CH2:14][C:13]=2[NH:12][C:11]([CH3:22])=[C:10]1[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 15035859Ethyl 9-(2,3-Dichlorophenyl)-1,1-dioxo-2,3,4,5,6,9-hexahydro-7-methylpyrido-[2,3-f][1,4]thiazepine-8-carboxylate

Product 1

HCID 15035860Ethyl 9-(2,3-Dichlorophenyl)-4,7-dimethyl-1,1-dioxo-2,3,4,5,6,9-hexahydropyrido-[2.3-f][1.41thiazepine-8-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of ethyl 9-(2,3-dichlorophenyl)-1,1-dioxo-2,3,4,5,6,9-hexahydro-7-methylpyrido-[2,3-f][1,4]thiazepine-8-carboxylate (0.500 g, 1.16 mmole) from Example 8, in acetonitrile (10 mL) was treated with formaldehyde (0.240 g, 37% aqueous solution) and sodium cyanoborohydride (0.062 g, 1.16 mmole). After 15 minutes, 6 drops of AcOH were added and the reaction was stirred for 1 hour. Then, 30 mL of water were added and the reaction mixture was extracted with 3×40 mL of chloroform. The pH was adjusted to 8 after the first extract. The combined organic extracts were dried with brine and Na2SO4 and then treated with 3 mL of triethylamine. After standing for 1.5 hours, the volatiles were removed under reduced pressure and the residue chromatographed (silica gel, 1.5% MeOH, 0.1% NH3 in CHCl3) to obtain the product as an oil which solidified on triturating with ether (0.479 g, 92% yield).

Workup

  1. extractionthe reaction mixture was extracted with 3×40 mL of chloroform
  2. dry with materialThe combined organic extracts were dried with brine and Na2SO4
  3. additiontreated with 3 mL of triethylamine
  4. waitAfter standing for 1.5 hours
  5. customthe volatiles were removed under reduced pressure
  6. customthe residue chromatographed (silica gel, 1.5% MeOH, 0.1% NH3 in CHCl3)

Sources & evidence

ORD record
ord-0b4a7547644f44709f79694f0d389413
Source dataset
uspto-grants-1991_12
Patent number
US05075440

Reaction notes

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