Ethyl Acetate → HCID 66718512, compound

HRID 1661766Notes

Reaction equation

HRID 1661766 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.[CH:30]1([C:33](Cl)=[O:34])[CH2:32][CH2:31]1.C(=O)([O-])O.[Na+].C(OCC)(=O)C>O1CCCC1>[CH:30]1([C:33]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:10]=2[C:9](=[O:11])[N:8]([C@@H:12]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=2)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]3)=[O:34])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 77637Cyclopropanecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 66718493HCID 66718493, compound

Product 1

HCID 66718512HCID 66718512, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (3R)-3-(7-amino-1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide (450 mg, 1 mmol) and cyclopropane carbonyl chloride (0.13 mL, 1.4 mmol) in tetrahydrofuran (5 mL) was heated to reflux for 15 min. 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) and 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, 1:1 ethyl acetate:methylene chloride) to give (3R)-3-[7-(cyclopropylcarbonylamino)-1-oxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropanamide as a white solid (0.35 g, 67% yield); mp, 92-94° C.; 1H NMR (CDCl3)˜0.82-0.89 (m, 2H, CH2), 1.05-1.11 (m, 2H, CH2), 1.43 (t, J=6.9 Hz, 3H, CH3), 1.64-1.70 (m, 1H, CH), 2.90 (s, 3H, CH3), 3.05 (dd, J=5.5, 16 Hz, 1H, CHH), 3.10 (s, 3H, CH3), 3.52 (dd, J=9.5, 15 Hz, 1H, CHH), 3.84 (s, 3H, CH3), 4.07 (q, J=7 Hz, 2H, CH2), 4.26 (d, J=17 Hz, 1H, CHH), 4.44 (d, J=17 Hz, 1H, CHH), 5.60 (dd, J=5.7, 9.4 Hz, 1H, NCH), 6.82 (d, J=8.7 Hz, 1H, Ar), 6.93-6.99 (m, 2H, Ar), 7.39 (t, J=7.9 Hz, 1H, Ar), 8.39 (d, J=8.2 Hz, 1H, Ar), 10.59 (s, 1H, NH); 13C NMR (CDCl3) δ 8.04, 14.64, 16.03, 35.46, 36.19, 37.31, 48.72, 53.56, 55.85, 64.46, 111.41, 112.52, 116.56, 117.41, 117.82, 119.13, 131.79, 132.84, 137.84, 141.54, 148.48, 149.04, 169.50, 169.58, 172.51; Anal Calcd for C26H31N3O5+0.5H2O: C, 65.81; H, 6.80; N, 8.85; H2O, 1.90. Found: C, 65.83; H, 6.72; N, 8.72; H2O, 1.94.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 min
  3. washThe organic layer was washed with sodium hydrogen carbonate (sat, 20 mL) and 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, 1:1 ethyl acetate:methylene chloride)

Sources & evidence

ORD record
ord-e28b5a85f6b64014862c1c8d5286e40b
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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