Methyl chloroformate → Methyl (8-acetylquinolin-2-yl)(phenyl)carbamate

HRID 1055876Notes

Reaction equation

HRID 1055876 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].Br[C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:13]=[CH:12]2.CCN(C(C)C)C(C)C.C1C[O:36][CH2:35][CH2:34]1>>[C:35]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([N:17]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:2](=[O:3])[O:4][CH3:5])[CH:13]=[CH:12]2)(=[O:36])[CH3:34]

Participants

5

Reactant 4

HCID 6586Methyl chloroformate2×HCID 8028TetrahydrofuranHCID 81531Diisopropylethylamine2×HCID 897821908-bromo-N-phenylquinolin-2-amine

Product 1

HCID 89793621Methyl (8-acetylquinolin-2-yl)(phenyl)carbamate

Conditions

Temperature
70 °C

Procedure

Methyl chloroformate (0.155 ml, 2.006 mmol) was added to a solution of 8-bromo-N-phenylquinolin-2-amine (Example 165c; 0.500 g, 1.671 mmol) and DIPEA (0.438 ml, 2.507 mmol) in 5 mL THF and stirred over the weekend. The reaction was then sealed and heated at 70° C. for 6 h. Additional DIPEA (0.438 ml, 2.507 mmol) and methyl chloroformate (0.155 ml, 2.006 mmol) were added and the reaction was stirred overnight at RT. The reaction was heated for several hours at 70° C. The reaction mixture was then quenched with saturated aq. NaHCO3 and diluted with DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by column chromatography (silica gel: 0-10% EtOAc/hexane). The product-containing fractions were concentrated under reduced pressure to afford a mixture of starting material and desired product (0.376 g) that was used in the next step without additional purification.

Workup

  1. customThe reaction was then sealed
  2. stirringthe reaction was stirred overnight at RT
  3. temperatureThe reaction was heated for several hours at 70° C
  4. customThe reaction mixture was then quenched with saturated aq. NaHCO3
  5. additiondiluted with DCM
  6. customThe organic layer was separated
  7. extractionthe aq. layer was extracted 3×DCM
  8. dry with materialThe combined organic layers were then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. additionThe material was treated with DCM
  12. custompurified by column chromatography (silica gel: 0-10% EtOAc/hexane)
  13. concentrationThe product-containing fractions were concentrated under reduced pressure
  14. customto afford

Sources & evidence

ORD record
ord-e519d5bae2b441328550d20ee1f24bda
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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