Boron Trichloride → HCID 135823107, compound

HRID 646490Notes

Reaction equation

HRID 646490 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][CH:12]=2)=[C:9]([C:24]2[CH:29]=[C:28]([CH2:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:27]([O:38]CC3C=CC=CC=3)=[CH:26][C:25]=2[O:46]CC2C=CC=CC=2)[O:8][N:7]=1)=[O:5])[CH3:2].B(Cl)(Cl)[Cl:55]>ClCCl>[ClH:55].[CH2:1]([NH:3][C:4]([C:6]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([CH2:17][N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[CH:15][CH:16]=2)=[C:9]([C:24]2[CH:29]=[C:28]([CH2:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:27]([OH:38])=[CH:26][C:25]=2[OH:46])[O:8][N:7]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 24773628HCID 24773628, compound

Product 1

HCID 135823107HCID 135823107, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-bath cooled solution of 5-(2,4-bis-benzyloxy-5-phenethyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide (0.109 g, 0.15 mmol) in dichloromethane (4 mL) under a nitrogen atmosphere was added a 1.0M solution of Boron trichloride in dichloromethane (0.45 mL; 0.45 mmol). The reaction mixture was stirred at 0° C. for 20 minutes then at ambient temperature for 3.5 hours. The reaction mixture was re-cooled to 0° C. and quenched by the addition of saturated aqueous sodium hydrogen carbonate solution (5 mL). After stirring for 5 minutes the dichloromethane was removed in vacuo and the residue was partitioned between ethyl acetate (20 mL) and water (20 mL). The phases were separated and the organic phase was washed with water (20 mL), saturated aqueous sodium chloride solution (20 mL) then dried over sodium sulphate. The mixture was filtered and the filtrate solvents were removed in vacuo to afford a light-brown oil which was purified by adsorption onto silica gel then flash chromatography on silica gel (10 g IST) eluting with 0 to 5% methanol in ethyl acetate. This affords a colourless oil which was triturated with 1.0M HCl in diethyl ether solution (5 mL) to afford 5-(2,4-dihydroxy-5-phenethyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide hydrochloride (0.019 g; 24%). LCMS: [M+H]+ 528. 1H NMR (400 MHz, d6-DMSO) □ 1.08 (t, 3H), 2.60 (m, 4H), 2.90-3.30 (m, 6H), 3.67 (m, 2H), 3.87 (m, 2H), 4.30 (s, 2H), 6.46 (s, 1H), 6.84 (s, 1H), 7.05-7.49 (m, 5H), 7.40-7.68 (m, 4H), 8.90 (brs, 1H), 9.67 (s, 1H), 9.89 (s, 1H), 10.75 (brs, 1H).

Workup

  1. waitat ambient temperature for 3.5 hours
  2. temperatureThe reaction mixture was re-cooled to 0° C.
  3. customquenched by the addition of saturated aqueous sodium hydrogen carbonate solution (5 mL)
  4. stirringAfter stirring for 5 minutes the dichloromethane
  5. customwas removed in vacuo
  6. customthe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  7. customThe phases were separated
  8. washthe organic phase was washed with water (20 mL), saturated aqueous sodium chloride solution (20 mL)
  9. dry with materialthen dried over sodium sulphate
  10. filtrationThe mixture was filtered
  11. customthe filtrate solvents were removed in vacuo
  12. customto afford a light-brown oil which
  13. customwas purified by adsorption onto silica gel
  14. washflash chromatography on silica gel (10 g IST) eluting with 0 to 5% methanol in ethyl acetate
  15. customThis affords a colourless oil which
  16. customwas triturated with 1.0M HCl in diethyl ether solution (5 mL)

Sources & evidence

ORD record
ord-86bdccef16724f42b9d44a73e755e14e
Source dataset
uspto-grants-2010_04
Patent number
US07705027B2

Reaction notes

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