Acetic Anhydride → HCID 60166734, compound

HRID 1485827Notes

Reaction equation

HRID 1485827 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](/[CH:21]=[CH:22]/[N+:23]([O-])=O)=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:32](OC(=O)C)(=[O:34])[CH3:33].C(N(CC)CC)C>C1COCC1.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:21][CH2:22][NH:23][C:32](=[O:34])[CH3:33])=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 21226445Aluminium lithium hydrideHCID 60166733HCID 60166733, compound

Product 1

HCID 60166734HCID 60166734, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Nitrostyrene 7a (182 mg, 0.55 mmol) in THF (0.7 mL) was added dropwise to a solution of Lithiumaluminium hydride (42 mg, 1.12 mmol) in THF (2 mL) under organ atmosphere at RT. Upon completion (nearly immediately) the reaction was quenched by the addition of water (42 μL), 3M NaOH (42 μL), and water (84 μL). The resulted mixture was filtered through a plug of celite, washed with DCM, and dried over K2CO3. Upon filtration the mixture was concentrated to oil and used without further purification. Acetic anhydride (58 μL, 0.62 mmol) and triethylamine (93 μL, 0.67 mmol) were added to a solution of the crude amine in DCM (5.6 mL) under an organ atmosphere at RT. After 3 h the reaction was quenched with saturated aqueous ammonium chloride and extracted with DCM (3×10 mL); combined organic fractions were washed with saturated aqueous sodiumchloride, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (SiO2; 3:1, Hex:EtOAc) to afford acetamide 8a (0.12 g, 0.35 mmol, 64%). 1H NMR (400 MHz, CDCl3) δ 7.50-7.38 (m, 8H), 7.38-7.30 (m, 2H), 7.23 (d, J=8.4 Hz, 1H), 7.01-6.95 (dd, J=8.4, 2.7 Hz, 1H), 6.93 (d, J=2.7 Hz, 1H), 5.71 (br s, NH), 5.08 (s, 2H), 3.42-3.16 (q, J=7.0 Hz, 2H), 2.89-2.64 (t, J=7.2 Hz, 2H), 1.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.2, 157.2, 143.4, 141.4, 137.0, 130.8, 129.1, 128.7, 128.6, 128.4, 128.0, 127.6, 127.2, 116.6, 114.2, 70.1, 40.7, 31.9, 23.2; HRMS m/z: [M+K+] for C23H23NO2K calcd, 384.1361. found, 384.1359.

Workup

  1. customUpon completion (nearly immediately) the reaction was quenched by the addition of water (42 μL), 3M NaOH (42 μL), and water (84 μL)
  2. filtrationThe resulted mixture was filtered through a plug of celite
  3. washwashed with DCM
  4. dry with materialdried over K2CO3
  5. filtrationUpon filtration the mixture
  6. concentrationwas concentrated to oil
  7. customused without further purification
  8. customAfter 3 h the reaction was quenched with saturated aqueous ammonium chloride
  9. extractionextracted with DCM (3×10 mL)
  10. washcombined organic fractions were washed with saturated aqueous sodiumchloride
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by column chromatography (SiO2; 3:1, Hex:EtOAc)

Sources & evidence

ORD record
ord-d930c853f5f549c1aa7b792b90c5d2ec
Source dataset
uspto-grants-2016_08
Patent number
US09422320B2

Reaction notes

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