Trifluoroacetic acid → 3-(4-Isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one

HRID 1478428Notes

Reaction equation

HRID 1478428 reaction equation
[CH2:1]1[C:6]2([O:11][CH:10]=[CH:9][C:8](=[O:12])[CH2:7]2)[CH2:5][CH2:4][NH:3][CH2:2]1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH:27]([O:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][C:32]=1[CH3:40])([CH3:29])[CH3:28]>C(Cl)Cl>[CH:27]([O:30][C:31]1[CH:39]=[CH:38][C:34]([C:35]([N:3]2[CH2:2][CH2:1][C:6]3([O:11][CH:10]=[CH:9][C:8](=[O:12])[CH2:7]3)[CH2:5][CH2:4]2)=[O:36])=[CH:33][C:32]=1[CH3:40])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 874026094-Isopropoxy-3-methyl-benzoyl chlorideHCID 897083431-Oxa-9-azaspiro[5.5]undec-2-en-4-one

Product 1

HCID 897085293-(4-Isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 11-oxa-3-azaspiro[5.5]undec-9-en-8-one; 2,2,2-trifluoroacetic acid (2.42 g, 8.6 mmol) in CH2Cl2 (35 mL) was added triethylamine (10.9 mL, 78.2 mmol) followed by the addition of 4-isopropoxy-3-methyl-benzoyl chloride (1.83 g, 8.60 mmol) in CH2Cl2 (5 mL) dropwise. The mixture was stirred at room temperature overnight. The mixture was diluted with CH2Cl2, washed with water, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (30-50% ethyl acetate-Hex) to provide 3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one (2.65 g) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.27 (t, J=4.0 Hz, 1H), 7.25-7.17 (m, 2H), 6.81 (d, J=8.1 Hz, 1H), 5.43 (d, J=6.1 Hz, 1H), 4.56 (dd, J=12.1, 6.0 Hz, 1H), 4.43-3.61 (m, 2H), 3.33 (s, 2H), 2.55 (s, 2H), 2.20 (s, 3H), 2.13 (d, J=13.2 Hz, 2H), 1.61 (s, 2H), 1.35 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 343.18, found 344.3 (M+1)+; Retention time: 1.50 minutes (3 minute run).

Workup

  1. washwashed with water
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe crude material was purified by column chromatography (30-50% ethyl acetate-Hex)

Sources & evidence

ORD record
ord-fac1e85c8a424f6896dce7d7a0d74924
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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