Boron Trichloride → 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-(morpholin-4-ylmethyl)phenyl)isoxazole-3-carboxamide

HRID 1891153Notes

Reaction equation

HRID 1891153 reaction equation
B(Cl)(Cl)Cl.[CH2:5]([NH:7][C:8]([C:10]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:17][CH:16]=2)=[C:13]([C:28]2[CH:33]=[C:32]([Cl:34])[C:31]([O:35]CC3C=CC=CC=3)=[CH:30][C:29]=2[O:43]CC2C=CC=CC=2)[O:12][N:11]=1)=[O:9])[CH3:6].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:5]([NH:7][C:8]([C:10]1[C:14]([C:15]2[CH:16]=[CH:17][C:18]([CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:19][CH:20]=2)=[C:13]([C:28]2[CH:33]=[C:32]([Cl:34])[C:31]([OH:35])=[CH:30][C:29]=2[OH:43])[O:12][N:11]=1)=[O:9])[CH3:6]

Participants

5

Reactant 3

HCID 25135Boron TrichlorideHCID 516892Sodium BicarbonateHCID 247741945-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide

Product 1

HCID 1355254165-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-(morpholin-4-ylmethyl)phenyl)isoxazole-3-carboxamideYield 64.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BCl3 (1M sol. in CH2Cl2, 3.87 ml, 3.87 mmol) was added dropwise to a solution of the crude 5-(2,4-Bis-benzyloxy-5-chloro-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide (810 mg, ˜1.29 mmol) in CH2Cl2 (30 ml) at 0° C. The reaction was then allowed to reach RT. Saturated aqueous NaHCO3 (40 ml) was then added slowly and the resultant mixture concentrated in vacuo. This was then partitioned between EtOAc (3×50 ml) and water (50 ml). The combined, dried (Na2SO4) organics were evaporated in vacuo. Flash chromatography eluting with CH2Cl2-10% MeOH/1% NH3/CH2Cl2 afforded 5-(5-Chloro-2,4-dihydroxy-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide (380 mg, 64% over 2 steps) as a yellow foam, LC/MS: RT=1.751 min. 458.2 (MH+).

Workup

  1. customto reach RT
  2. concentrationthe resultant mixture concentrated in vacuo
  3. customThis was then partitioned between EtOAc (3×50 ml) and water (50 ml)
  4. dry with materialdried (Na2SO4)
  5. customorganics were evaporated in vacuo
  6. washFlash chromatography eluting with CH2Cl2-10% MeOH/1% NH3/CH2Cl2

Sources & evidence

ORD record
ord-ebcc5b2ac39148deb62940c194abd882
Source dataset
uspto-grants-2013_08
Patent number
US08507480B2

Reaction notes

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