Triethylamine → (S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-7-nitroisoindolin-1-one

HRID 1019520Notes

Reaction equation

HRID 1019520 reaction equation
CO[C:3](=[O:15])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:13]Br.[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([C@H:27]([NH2:33])[CH2:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[CH3:17].C(N(CC)CC)C>CN(C=O)C.CCOCC>[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([C@H:27]([N:33]2[CH2:13][C:5]3[C:4](=[C:9]([N+:10]([O-:12])=[O:11])[CH:8]=[CH:7][CH:6]=3)[C:3]2=[O:15])[CH2:28][S:29]([CH3:32])(=[O:31])=[O:30])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[CH3:17]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11282264(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineHCID 21708527Methyl 2-(bromomethyl)-6-nitrobenzoate

Product 1

HCID 58224189(S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-7-nitroisoindolin-1-oneYield 54.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-bromomethyl-6-nitro-benzoic acid methyl ester (4.0 g, 14.6 mmol), (1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (4.0 g, 14.6 mmol) and triethylamine (4.4 mL, 31.6 mmol) in DMF (40 mL) was heated at 80° C.-90° C. for 1 day. The solvent was removed in vacuo to give an oil. The oil was extracted with ethyl acetate (150 mL) and HCl (2N, 50 mL). The organic layer was washed with HCl (2N, 2×50 mL), water (2×50 mL), brine (2×50 mL) and dried over MgSO4. The solvent was removed in vacuo to give a yellow oil. The oil was slurried in ether (50 mL) to give a suspension. The suspension was filtered and washed with ether to give 2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-nitro-2,3-dihydro-isoindol-1-one as a yellow solid (3.43 g, 54% yield): 1H NMR (CDCl3) δ 1.5 (t, J=7 Hz, 3H, CH3), 2.99 (s, 3H, CH3), 3.69 (dd, J=5, 15 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.07 (q, J=7 Hz, 2H, CH2), 4.27 (dd, J=11, 15 Hz, 1H, CHH), 4.30 (d, J=17 Hz, 1H, NCHH), 4.54 (d, J=17 Hz, 1H, NCHH), 5.70 (dd, J=5, 10 Hz, 1H, NCH), 6.85 (d, J=8 Hz, 1H, Ar), 6.94-7.00 (m, 2H, Ar), 7.58-7.76 (m, 3H, Ar).

Workup

  1. customThe solvent was removed in vacuo
  2. customto give an oil
  3. extractionThe oil was extracted with ethyl acetate (150 mL) and HCl (2N, 50 mL)
  4. washThe organic layer was washed with HCl (2N, 2×50 mL), water (2×50 mL), brine (2×50 mL)
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customto give a yellow oil
  8. customto give a suspension
  9. filtrationThe suspension was filtered
  10. washwashed with ether

Sources & evidence

ORD record
ord-0b94e5cae27b44b390294e24374a301c
Source dataset
uspto-grants-2014_05
Patent number
US08716252B2

Reaction notes

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