Ethyl Acetate → HCID 66718512, compound

HRID 2282975Notes

Reaction equation

HRID 2282975 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-28cfb5ab34fe419abd18018e89094bef
Source dataset
uspto-grants-2015_09
Patent number
USRE045685E1

Reaction notes

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