Ethyl Acetate → HCID 86596516, compound

HRID 1744304Notes

Reaction equation

HRID 1744304 reaction equation
[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=2[F:19])=[C:7]([CH3:20])[N:6]([CH2:21][C:22]2[C:27]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:25]=[CH:24][C:23]=2[F:32])[C:5]1=[O:33].C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:47][CH2:48][CH2:49][N:50]1[C:54](=[O:55])[C:53]2=[CH:56][CH:57]=[CH:58][CH:59]=[C:52]2[C:51]1=[O:60].C(OCC)(=O)C>CN(C=O)C>[C:51]1(=[O:60])[N:50]([CH2:49][CH2:48][CH2:47][NH:1][C@H:2]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:3][N:4]2[C:9](=[O:10])[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[C:12]=3[F:19])=[C:7]([CH3:20])[N:6]([CH2:21][C:22]3[C:27]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:25]=[CH:24][C:23]=3[F:32])[C:5]2=[O:33])[C:54](=[O:55])[C:53]2=[CH:56][CH:57]=[CH:58][CH:59]=[C:52]12

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 21611N-3-BromopropylphthalimideHCID 11364940HCID 11364940, compound

Product 1

HCID 86596516HCID 86596516, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of compound 6d (4.0 g, 7.2 mmol) in anhydrous DMF (8 mL) was added sodium carbonate (0.76 g, 7.2 mmmol) and N-(3-bromopropyl)phthalimide (2.4 g, 9.0 mmmol). The reaction mixture was heated to 80° C. under nitrogen for 4 hr. The reaction mixture was cooled and partitioned between dichloromethane and water. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine, dried with sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel, eluting with dichloromethane, 50% ethyl acetate in hexane and then ethyl acetate to yield 6e as a pale yellow solid (3.6 g, 4.9 mmol, 67%). MS (CI) m/z 743.1 (M+H+), tR=2.539 min. (method 4). 1H NMR (CDCl3): δ 1.62–1.70 (m, 2H), 2.26 (s, 1.5H), 2.27 (s, 1.5H), 2.29–2.33 (m, 1H), 2.40–2.48 (m, 1H), 3.51 (s, 1.5H), 3.52 (s, 1.5H), 3.54–3.74 (m, 2H), 3.90 (s, 1.5H), 3.91 (s, 1.5H), 3.93–4.26 (m, 3H), 5.60 (brs, 2H), 6.80–6.89 (m, 1H), 6.99 (dd, 1H), 7.11–7.36 (m, 8H), 7.42–7.49 (m, 1H), 7.71–7.75 (m, 2H), 7.84–7.89 (m, 1H), 7.95 (d, J=8.4 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between dichloromethane and water
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel
  8. washeluting with dichloromethane, 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-46c1adc0583a478fb9122ee4c97d4328
Source dataset
uspto-grants-2006_03
Patent number
US07015226B2

Reaction notes

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