Potassium Carbonate → Tert-butyl ((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

HRID 445399Notes

Reaction equation

HRID 445399 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1[S:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[N:12][N:13]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=1)[CH2:32]Br>CN(C)C=O>[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1[S:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:32][C:31]3[CH:34]=[CH:35][CH:36]=[C:29]([F:28])[CH:30]=3)=[CH:18][CH:19]=2)=[N:12][N:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 680073-Fluorobenzyl bromideHCID 136340687Tert-butyl ((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

Product 1

HCID 86663647Tert-butyl ((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(5-(aminomethyl)-1,3,4-thiadiazol-2-yl)phenol (1 g, 3.5 mmol) in methanol (9 mL) containing NaHCO3 (1.2 g, 13.9 mmol) and di-t-butyldicarbonate (Boc2O; 1.5 g, 7.0 mmol) was stirred for 5 h. The resulting mixture was filtered and the filtrate concentrated. The residue was dissolved in CH2Cl2 (48 mL) and treated with 0.5 M NaOCH3 in methanol (8.3 mL). After stirring at room temperature for 1 h, the volatiles were removed under vacuum to yield tert-butyl ((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate. To a solution of tert-butyl((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate (1.01 g, 2.89 mmol), dimethylformamide (16 mL) and potassium carbonate (1.36 g, 9.86 mmol) was added 3-fluorobenzylbromide (0.61 mL, 4.93 mmol), and the mixture was stirred at room temperature overnight. After 24 h, the resulting mixture was filtered and the filtrate was concentrated. The residue was purified by chromatography (silica gel, heptane:EtOAc) to yield tert-butyl((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)carbamate. 1H NMR (400 MHz, CDCl3) δ 7.87-7.92 (m, 2H), 7.33-7.42 (m, 1H), 7.14-7.23 (m, 2H), 7.01-7.08 (m, 3H), 5.13 (s, 2H), 4.68-4.77 (m, 2H), and 1.48 (s, 9H); MS (ES+) 416 (M+1).

Workup

  1. waitAfter 24 h
  2. filtrationthe resulting mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by chromatography (silica gel, heptane:EtOAc)

Sources & evidence

ORD record
ord-6e64e49caced4f94b996330ea8322111
Source dataset
uspto-grants-2013_07
Patent number
US08476302B2

Reaction notes

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