Triethylamine → Dibenzyl ether

HRID 584571Notes

Reaction equation

HRID 584571 reaction equation
[CH2:1](N(CC)CC)C.[CH2:8]([O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:16]([O:15][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:21]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:1]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 27343144-Benzyloxy-phenylboronic acid

Product 1

HCID 7657Dibenzyl etherYield 56.9%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

The sultam 3 (R2, R3=H; R10=t-Bu; n=2) (198 mg) was dissolved in methylene chloride along with copper (II) acetate (153 mg), triethylamine (426 mg), 4 Å molecular sieves (180 mg), and 4-benzyloxybenzeneboronic acid (384 mg). The reaction was stirred open to air for 3 days. The mixture was filtered and concentrated. Purification of the crude material by silica gel chromatography (10-45% ethyl acetate/hexanes) provided the sulfonamide 4 (R2, R3=H; R=4-benzyloxyphenyl; R10=t-Bu; n=2) (190 mg, 54%). MS found: (M+Na+MeCN)+=481. (39b) The sulfonamide 4 (R2, R3=H; R=4-benzyloxyphenyl; R10=t-Bu; n=2) (190 mg) was dissolved in methanol prior to the addition of 20% Pd(OH)2/C (20 mg). A hydrogen balloon was added, and the solution was stirred overnight. The hydrogen balloon was removed, and the solution was filtered and concentrated. This gave the phenol 4 (R2, R3=H; R=4-hydroxyphenyl; R10=t-Bu; n=2) (quant.) ready for subsequent reactions. MS found: (M+Na+MeCN)+=391. (39c) A solution of phenol 4 (R2, R3=H; R=4-hydroxyphenyl; R10=t-Bu; n=2) (149 mg), potassium carbonate (314 mg), and 2-methyl-4-chloromethylquinoline (87 mg) in acetonitrile was heated at reflux for 2 hr. The solution was cooled to rt, filtered, and concentrated. The crude material was purified by silica gel chromatography (20-65% acetonitrile/water) to provide ester 4 (R2, R3=H; R=4-[(2-methyl-4-quinolinyl)methoxy]phenyl; R10=t-Bu; n=2) (140 mg) MS found: (M+H)+=483. (39d) To a solution of ester 4 (R2, R3=H; R=4-[(2-methyl-4-quinolinyl)methoxy]phenyl; R10=t-Bu; n=2) (140 mg) in methanol was added thionyl chloride (3.0 g). The mixture was allowed to stir for 1 h and concentrated to give methyl ester 4 (R2, R3=H; R=4-[(2-methyl-4-quinolinyl)methoxy]phenyl; R10=Me; n=2) (quant.). MS found: (M+H)+=441. (39e) The ester 4 (R2, R3=H; R=4-[(2-methyl-4-quinolinyl)methoxy]phenyl; R10=Me; n=2) (128 mg) was treated as in (35b) to yield the title hydroxamate 5 (R2, R3=H; R=4-[(2-methyl-4-quinolinyl)methoxy]phenyl; n=2) (15 mg). MS found: (M+H)+=442.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customPurification of the crude material by silica gel chromatography (10-45% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-202958442ac94cf18b7cfe24901257bb
Source dataset
uspto-grants-2005_08
Patent number
US06927216B2

Reaction notes

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