Trifluoroacetic acid → 3-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

HRID 2191423Notes

Reaction equation

HRID 2191423 reaction equation
C([O:5][C:6]([C:8]1[NH:17][C:16]2[CH2:15][CH2:14][CH2:13][N:12]([CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[C:11](=[O:26])[C:10]=2[C:9]=1[CH3:27])=O)(C)(C)C.FC(F)(F)C(O)=O.C(OC(OCC)OCC)C>>[CH3:27][C:9]1[C:10]2[C:11](=[O:26])[N:12]([CH2:18][CH2:19][N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[CH2:13][CH2:14][CH2:15][C:16]=2[NH:17][C:8]=1[CH:6]=[O:5]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 31214Ethyl orthoformateHCID 592500943-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester

Product 1

HCID 592500683-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehydeYield 40.9%

Procedure

3-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 10b (725 mg, 1.92 mmol) was dissolved in trifluoroacetic acid (2.6 ml, 34.2 mmol) in an ice-water bath under stirring. The reaction mixture was stirred at 40° C. in a water bath for 5 minutes, added with triethoxy methane (0.42 ml, 2.5 mmol) in one portion at −5° C. in an ice-water bath, and stirred for 2 minutes. Then the ice-salt bath was removed, and the reaction mixture was allowed to warm up to room temperature, became brown and stirred for another 2 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with a little water, adjusted to pH 8 with dilute sodium hydroxide solution (2 mol/L) and extracted with dichloromethane (50 ml×3). The combined organic extracts were concentrated under reduced pressure to obtain henna solid. The solid was purified by silica gel column chromatography to obtain the title compound 3-methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 10c (240 mg, yield 40%) as a light yellow solid.

Workup

  1. stirringThe reaction mixture was stirred at 40° C. in a water bath for 5 minutes
  2. stirringstirred for 2 minutes
  3. customThen the ice-salt bath was removed
  4. stirringstirred for another 2 hours
  5. customthe reaction mixture was quenched with a little water
  6. extractionextracted with dichloromethane (50 ml×3)
  7. concentrationThe combined organic extracts were concentrated under reduced pressure
  8. customto obtain henna solid
  9. customThe solid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5f30ec12722442679f79f46f2e2d2a96
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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