Triethylamine → HCID 57344633, compound

HRID 2401399Notes

Reaction equation

HRID 2401399 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[CH:10]([NH2:23])[N:9]=2)=[CH:4][CH:3]=1.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26].C(N(CC)CC)C>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[CH:10]([NH:23][C:25](=[O:26])[O:27][CH2:28][CH3:29])[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 57344512HCID 57344512, compound

Product 1

HCID 57344633HCID 57344633, compoundYield 45.2%

Conditions

Temperature
0 °C

Procedure

To a round bottomed flask was added 6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-amine (218 mg, 0.67 mmol). The flask was purged with nitrogen, MeCN was added (7 mL), and the solution was cooled to 0° C. Ethyl chloroformate (78 μL, 0.81 mmol) and triethylamine (122 μL, 0.88 mmol) were added and the reaction was allowed to warm to ambient temperature and stirred for 2 h. The reaction was quenched with a 1:1 mixture of sat. aq. NaHCO3:brine and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, concentrated and purified on a Biotage (isocratic elution 25% EtOAc: 75% Hexanes) to provide the title compound as white solid (120 mg). The enantiomers were separated by chrial SFC using a 3.0×25.0 cm RegisPack column, with 35% cosolvent (1:1 MeOH:i-PrOH), 80 mL/min at 100 bar. Rention time peak 1 (compound 253): 1.48 min, 100% ee. Retention time peak 2 (compound 254): 2.96 min, 98.1% ee.

Workup

  1. customThe flask was purged with nitrogen, MeCN
  2. additionwas added (7 mL)
  3. temperatureto warm to ambient temperature
  4. customThe reaction was quenched with a 1:1 mixture of sat. aq. NaHCO3
  5. extractionbrine and extracted with EtOAc
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on a Biotage (isocratic elution 25% EtOAc: 75% Hexanes)

Sources & evidence

ORD record
ord-a46814c7eea7479db9cb10d6f1c0bb55
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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