Dichloromethane → 4-{[(Dibutylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate

HRID 1798414Notes

Reaction equation

HRID 1798414 reaction equation
S=C1N([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18](=[O:20])[CH3:19])=[C:13]([O:21][CH3:22])[CH:12]=2)=[O:8])CCS1.[CH2:23]([NH:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH3:26].C(N(CC)CC)C.C(N(C(C)C)CC)(C)C.[Cl:48][CH2:49][Cl:50]>C1COCC1>[Cl:48][CH2:49][Cl:50].[CH:18]([O:17][CH:14]([CH3:13])[CH3:15])([CH3:19])[CH3:23].[C:18]([O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][O:9][C:7](=[O:8])[N:27]([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:12][C:13]=1[O:21][CH3:22])(=[O:20])[CH3:19]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 8148Dibutylamine2×HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 568478684-(Acetyloxy)-3-methoxybenzyl 2-thioxo-1,3-thiazolidine-3-carboxylate

Product 2

HCID 22238436Dichloromethane diisopropyletherHCID 568479174-{[(Dibutylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetateYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A yellow solution of VII (159.9 mg, 0.468 mmol), di-n-butylamine (64 mg, 83 μL, 1.05×0.468 mmol) and triethylamine (47 mg, 65 μL, 0.468 mmol) in 2.5 mL of dry THF was stirred at room temperature overnight. One equivalent of diisopropylethylamine and 0.5 equivalent of dibutylamine were added, and stirring continued for three days. The solution was diluted with dichloromethane and extracted with 1N HCl and then saturated NaCl. The organic layer was dried over MgSO4, filtered and concentrated. The crude material was covered with 5 mL of 7:3 hexanes/ethyl acetate solution and a few drops of ethyl acetate to render a solution. Upon standing overnight, much of the mercaptothiazoline crystallized out. The supernatant was withdrawn, and the crystals were rinsed with a small portion of 7:3 hexanes/ethyl acetate. The combined organic layer was concentrated and redissolved in dichloromethane/diisopropyl ether (86:14, v/v). Column chromatography on silica gel eluting with dichloromethane/diisopropyl ether (86:14, v/v) gave 113.9 mg (69%) of 7 as a clear oil: Rf=0.72 (dichloromethane/diisopropyl ether, 86:14, v/v); 1HNMR (CDCl3) δ 6.98 (d, 3J=8.0 Hz, 1H), 6.95 (d, 4J=1.65 Hz, 1H), 6.90 (dd, 3J=8.0 Hz, 4J=1.75 Hz, 1H), 5.07 (s, 2H), 3.80 (s, 3H), 3.24-3.18 (m, 4H), 2.29 (s, 3H), 1.53-1.43 (m, 4H), 1.32-1.21 (m, 4H) and 0.92-0.85 (m, 6H). Exact mass (FAB+) calculated for C19H30NO5 [M+H] 352.2118. found 352.2115.

Workup

  1. extractionextracted with 1N HCl
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. waitUpon standing overnight, much of the mercaptothiazoline
  6. customcrystallized out
  7. customThe supernatant was withdrawn
  8. washthe crystals were rinsed with a small portion of 7:3 hexanes/ethyl acetate
  9. concentrationThe combined organic layer was concentrated
  10. dissolutionredissolved in dichloromethane/diisopropyl ether (86:14

Sources & evidence

ORD record
ord-bc5721326bb24763b8acb99c81a43430
Source dataset
uspto-grants-2013_01
Patent number
US08343971B2

Reaction notes

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