Acetic Acid → HCID 67073291, compound

HRID 913189Notes

Reaction equation

HRID 913189 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]([CH:12]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:7]2.[CH:29]1([CH:32]=O)[CH2:31][CH2:30]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:29]1([CH2:32][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:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=2)[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH2:7]3)[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 18758337HCID 18758337, compound

Product 1

HCID 67073291HCID 67073291, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 7-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (1.8 g, 4.5 mmol), cyclopropane carboxaldehyde (0.47 mL, 6.3 mmol), and acetic acid (1.6 mL, 28 mmol) in 1,2-dichloroethane (20 mL), was added sodium triacetoxyborohydride (1.4 g, 6.7 mmol) at room temperature. After 1.5 hours, the mixture was extracted with methylene chloride (50 mL) and water (20 mL). The organic layer was washed with sodium hydrogen carbonate (sat, 25 mL) and brine (25 mL), and dried over MgSO4. Removal of solvent gave a yellow oil, which was purified by prep HPLC to give (1S)-7-(Cyclopropylmethyl-amino)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one as a white solid (1.6 g, 79% yield): mp 147-149° C.; 1H NMR (CDCl3) δ 0.25-0.31 (m, 2H, CH2), 0.55-0.62 (m, 2H, CH2), 1.09-1.20 (m, 1H, CH), 1.45 (t, J=7 Hz, 3H, CH3), 2.93 (s, 3H, CH3), 3.03-3.08 (m, 2H, CH2), 3.67 (dd, J=5, 15 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.08 (q, J=7 Hz, 2H, CH2), 4.18 (d, J=17 Hz, 1H, CHH), 4.29 (dd, J=10, 15 Hz, 1H, CHH), 4.34 (d, J=17 Hz, 1H, CHH), 5.62 (dd, J=5, 10 Hz, 1H, NCH), 6.47-6.55 (m, 2H, Ar), 6.69 (t, J=5 Hz, 1H, NH), 6.83 (d, J=8 Hz, 1H, Ar), 6.91-6.95 (m, 2H, Ar), 7.21-7.30 (m, 1H, Ar); 13C NMR (CDCl3) δ 3.57, 10.63, 14.71, 41.42, 47.52, 48.09, 52.04, 55.98, 56.39, 64.60, 108.35, 109.21, 111.48, 112.32, 113.77, 119.37, 130.45, 133.64, 142.78, 147.50, 148.79, 149.54, 171.16. Analy. calculated for C24H30N2O5S: C, 62.86; H, 6.59; N, 6.11. Found: C, 62.77; H, 6.62; N, 6.13.

Workup

  1. extractionthe mixture was extracted with methylene chloride (50 mL) and water (20 mL)
  2. washThe organic layer was washed with sodium hydrogen carbonate (sat, 25 mL) and brine (25 mL)
  3. dry with materialdried over MgSO4
  4. customRemoval of solvent
  5. customgave a yellow oil, which
  6. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-78b217eaba7b46ef84d31b99fd12cbae
Source dataset
uspto-grants-2011_09
Patent number
US08026269B2

Reaction notes

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