Sodium hydride → HCID 22237418, compound

HRID 1743446Notes

Reaction equation

HRID 1743446 reaction equation
[H-].[Na+].[CH3:3][O:4][CH2:5][O:6][C:7]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:11][C:10]([C:20](=[O:28])[NH:21][CH2:22][C:23]2([CH2:26][OH:27])[CH2:25][CH2:24]2)=[CH:9][C:8]=1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=1.C1OCCOCCOCCOCCOC1.[C:51]1([CH2:57][CH2:58][CH2:59][CH2:60]Br)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[CH3:3][O:4][CH2:5][O:6][C:7]1[C:8]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=2)=[CH:9][C:10]([C:20](=[O:28])[NH:21][CH2:22][C:23]2([CH2:26][O:27][CH2:60][CH2:59][CH2:58][CH2:57][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH2:24][CH2:25]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 2596681-Bromo-4-phenylbutaneHCID 22237592HCID 22237592, compound

Product 1

HCID 22237418HCID 22237418, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a round bottom flask with NaH (0.201 g, 5.03 mmol) and THF (50 mL) cooled to 0° C. was added (3,3″-dichloro-5′-{[1-(hydroxymethyl)-cyclopropylmethyl]-carbamoyl}-[1,1′;3′1″]terphenyl-2′-yloxy)methyl methyl ether (1.88 g, 3.87 mmol). The resulting solution was heated to reflux for 10 min. and then cooled back to room temperature. To this solution was added 15-crown-5 (0.308 mL, 1.55 mmol), tetrabutylammonium iodide (0.573 g, 1.55 mmol), and finally 4-phenyl-butylbromide (3.30 g, 15.5 mmol) in THF (10 mL). The final mixture was heated to reflux for 18 h. At this point, the reaction mixture was quenched with MeOH (10 mL) and then diluted with EtOAc (400 mL). The organic layer was washed with 1 N HCl (40 mL), sat. aq. NaHCO3 (40 mL), and brine (40 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 30% EtOAc/petroleum ether gradient) to afford the product (0.777 g, 33%) as a solid; 1H NMR (CDCl3) δ 0.48–0.58 (m, 2H), 0.58–0.67 (m, 2H), 1.47–1.56 (m, 4H), 2.40 (t, J=7.5 Hz, 2H), 2.73 (s, 3H), 3.38 (s, 2H), 3.38–3.48 (m, 4H), 4.40 (s, 2H), 7.07 (d, J=7.5 Hz, 2H), 7.12–7.26 (m, 3H), 7.31–7.42 (m, 4H), 7.42–7.53 (m, 3H), 7.62 (s, 2H), 7.77 (s, 2H); mass spectrum [(+) ESI], m/z 618 (M)+.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 10 min.
  3. temperatureto reflux for 18 h
  4. customAt this point, the reaction mixture was quenched with MeOH (10 mL)
  5. additiondiluted with EtOAc (400 mL)
  6. washThe organic layer was washed with 1 N HCl (40 mL), sat. aq. NaHCO3 (40 mL), and brine (40 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationAfter concentration
  9. customthe residue was purified by the Biotage Flash 40 apparatus (10 to 30% EtOAc/petroleum ether gradient)

Sources & evidence

ORD record
ord-ba06a24195a4483880d209848e218919
Source dataset
uspto-grants-2006_03
Patent number
US07008636B2

Reaction notes

Loading…