Water → HCID 178453976, compound

HRID 1445352Notes

Reaction equation

HRID 1445352 reaction equation
[C:1]1([CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(Cl)Cl.[C:12]([O:16][C:17]([NH:19][C@H:20]1[CH2:25]C[C@H](N)[CH2:22][CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C([N:29]([CH2:32][CH3:33])[CH2:30]C)C.[OH2:34]>>[C:12]([O:16][C:17]([NH:19][C@H:20]1[CH2:25][CH2:33][C@H:32]([N:29]2[CH2:30][C:6]3[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:7]2=[O:34])[CH2:22][CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 5

HCID 962WaterHCID 1140TolueneHCID 6212ChloroformHCID 8471TriethylamineHCID 178419079HCID 178419079, compound

Product 1

HCID 178453976HCID 178453976, compound

Conditions

Temperature
100 °C

Procedure

15 ml of toluene-1.5 ml of chloroform solution containing 500 mg of N-tert-butoxycarbonyl-trans-1,4-cyclohexanediamine, 623 mg of ethyl 2-bromomethyl benzoate and 354 mg of triethylamine was heated at 100° C. for 5 hours. After cooling, water was added to the mixture and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography to obtain 400 mg of N-tert-butoxycarbonyl-trans-4-(1-oxo-2-isoindolinyl)cyclohexylamine. (2) 10 ml of 4N HCl/dioxane was added to 10 ml of a dioxane solution containing 380 mg of the compound obtained in the above (1), and the mixture was stirred at room temperature for 5 hours. After the reaction mixture was concentrated, the residue was triturated with diethyl ether to obtain 298 mg of trans-4-(1-oxo-2-isoindolinyl)cyclohexylamine hydrochloride (Reference Example 8-24 in Table 9).

Workup

  1. temperatureAfter cooling
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-35d4897e21ff47aea85b631e54d20b2b
Source dataset
uspto-grants-2010_02
Patent number
US07666869B2

Reaction notes

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