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

HRID 1461482Notes

Reaction equation

HRID 1461482 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][CH2:27][O:28][C:29](=[O:31])[CH3:30])=[O:24].C=O.[C:34]([BH3-])#N.[Na+].[OH-].[Na+]>C(#N)C.O.C(O)(=O)C>[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]([CH3:34])[CH2:14][C:13]=2[NH:12][C:11]([CH3:22])=[C:10]1[C:23]([O:25][CH2:26][CH2:27][O:28][C:29](=[O:31])[CH3:30])=[O:24]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 150358802-Acetoxyethyl 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 150358782-Acetoxyethyl 9-(2,3-Dichlorophenyl)-4,7-dimethyl-1,1-dioxo-2,3,4,5,6,9-hexahydropyrido[2,3-f][1,4]thiazepine-8-carboxylateYield 87.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-acetoxyethyl 9-(2,3-dichlorophenyl) -1,1-dioxo-2,3,4,5,6,9-hexahydro-7-methyl-pyrido[2,3-f][1,4]thiazepine-8-carboxylate (0.880 g, 1.69 mmole) from Example 19, and 1 mL of 38% aqueous formaldehyde solution in 20 mL of acetonitrile was treated with sodium cyanoborohydride (0.070 g, 1.69 mmole). After stirring for 1 hour, 0.5 mL of acetic acid was added, and the reaction was stirred for another 2 hours. After the addition of 40 mL of water and adjustment of the pH to 9 with 6N sodium hydroxide, the reaction was extracted with 3×30 mL of chloroform. The combined organic extracts were dried with sodium sulfate, the solvent was removed under reduced pressure, and the residue was chromatographed (2% methanol, 0.1% ammonia in chloroform on silica gel) to obtain the title compound (0.743 g, 82%).

Workup

  1. stirringthe reaction was stirred for another 2 hours
  2. extractionthe reaction was extracted with 3×30 mL of chloroform
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customthe residue was chromatographed (2% methanol, 0.1% ammonia in chloroform on silica gel)

Sources & evidence

ORD record
ord-c74c189e2aa54a64b8a490365d2baff7
Source dataset
uspto-grants-1991_12
Patent number
US05075440

Reaction notes

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