Acetyl chloride → HCID 66718504, compound

HRID 433305Notes

Reaction equation

HRID 433305 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2.[C:30](Cl)(=[O:32])[CH3:31].C(=O)([O-])O.[Na+].C(OCC)(=O)C>O1CCCC1>[C:30]([NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2)(=[O:32])[CH3:31]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 66718493HCID 66718493, compound

Product 1

HCID 66718504HCID 66718504, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred mixture of (3R)-3-(7-amino-1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide (400 mg, 1 mmol) and acetyl chloride (0.1 mL, 1.4 mmol) in tetrahydrofuran (5 mL) was heated to reflux for 2 h. To the mixture was added 50% sodium hydrogen carbonate (40 mL) and ethyl acetate (50 mL). The organic layer was washed with sodium hydrogen carbonate (sat, 20 mL), brine (20 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give an oil. The oil was purified by column chromatography (Silica Gel, 1.5:1 ethyl acetate:methylene chloride) to give (3R)-3-[7-(acetylamino)-1-oxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide as a white solid (0.25 g, 57% yield); mp, 88-90° C.; 1H NMR (CDCl3) ˜1.43 (t, J=6.9 Hz, 3H, CH3), 2.22 (s, 3H, CH3), 2.90 (s, 3H, CH3), 3.04 (dd, J=5.5, 16 Hz, 1H, CHH), 3.09 (s, 3H, CH3), 3.52 (dd, J=9.5, 15 Hz, 1H, CHH), 3.84 (s, 3H, CH3), 4.07 (q, J=7.1 Hz, 2H, CH2), 4.26 (d, J=17 Hz, 1H, CHH), 4.44 (d, J=17 Hz, 1H, CHH), 5.58 (dd, J=5.5, 9.4 Hz, 1H, NCH), 6.81-6.84 (m, 1H, Ar), 6.92-7.01 (m, 3H, Ar), 7.41 (t, J=7.8 Hz, 1H, Ar), 8.41 (d, J=8.3 Hz, 1H, Ar), 10.37 (s, 1H, NH); 13C NMR (CDCl3) ˜14.65, 24.84, 35.47, 36.16, 37.31, 48.71, 53.54, 55.85, 64.44, 111.35, 112.44, 116.83, 117.40, 117.97, 119.10, 131.72, 132.84, 137.65, 141.53, 148.46, 149.06, 168.98, 169.41, 169.57; Anal Calcd for C24H29N3O5+0.7 H2O: C, 63.76; H, 6.78; N, 9.29; H2O, 2.79. Found: C, 63.89; H, 6.64; N, 9.14; H2O, 2.70.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. washThe organic layer was washed with sodium hydrogen carbonate (sat, 20 mL), brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customto give an oil
  7. customThe oil was purified by column chromatography (Silica Gel, 1.5:1 ethyl acetate:methylene chloride)

Sources & evidence

ORD record
ord-5720adff7d684c9e97c71f9b1aab1a36
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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