Acetyl chloride → N-(4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-yl)acetamide

HRID 1774363Notes

Reaction equation

HRID 1774363 reaction equation
[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23]C(=O)OC(C)(C)C)[CH:18]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:31](O)([C:33](F)(F)F)=[O:32].CCN(C(C)C)C(C)C.C(Cl)(=O)C>C(Cl)Cl.C([O-])(O)=O.[Na+].C1COCC1>[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:31](=[O:32])[CH3:33])[CH:18]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

8

Reactant 4

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 58416756tert-Butyl 4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate

Product 1

HCID 67457565N-(4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-yl)acetamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of tert-butyl 4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate (900 mg, 2.20 mmol) in DCM (10.0 mL) was added TFA (10.0 mL) and the reaction mixture was stirred at RT overnight. The resulting mixture was evaporated in vacuo and the residue subjected to SCX capture and release. The crude product so obtained was taken up into THF (8.0 mL) and DIPEA (660 μl, 3.8 mmol) and then acetyl chloride (147 μl, 2.06 mmol) were added. After stirring for 1 hr, the mixture was diluted with saturated aq. NaHCO3 (10.0 mL) and was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine and then dried, and evaporated in vacuo. The residue was taken up in a mixture of acetonitrile and a solution of NH3 in MeOH (7M, 1:1 v/v, 20 mL) and after 10 min was re-evaporated in vacuo. The residue was triturated with MeOH (10.0 mL) to afford N-(4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-yl)acetamide, as a yellow solid (570 mg, 74%): m/z 352 (M+H)+ (ES+).

Workup

  1. customThe resulting mixture was evaporated in vacuo
  2. customThe crude product so obtained
  3. stirringAfter stirring for 1 hr
  4. extractionwas extracted with EtOAc (2×20 mL)
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. customevaporated in vacuo
  8. additionThe residue was taken up in a mixture of acetonitrile
  9. customa solution of NH3 in MeOH (7M, 1:1 v/v, 20 mL) and after 10 min was re-evaporated in vacuo
  10. customThe residue was triturated with MeOH (10.0 mL)

Sources & evidence

ORD record
ord-c39b10fd1d244aa79f1c7965d93bd2a3
Source dataset
uspto-grants-2016_02
Patent number
US09260410B2

Reaction notes

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