Benzyl Bromide → 5,6,7,8-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-4H-thiazolo[5,4-c]azepin-4-one

HRID 1529568Notes

Reaction equation

HRID 1529568 reaction equation
[H-].[Na+].[O:3]([CH2:10][C:11]1[S:12][C:13]2[C:14](=[O:21])[NH:15][CH2:16][CH2:17][CH2:18][C:19]=2[N:20]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C.O>[O:3]([CH2:10][C:11]1[S:12][C:13]2[C:14](=[O:21])[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:16][CH2:17][CH2:18][C:19]=2[N:20]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 532467235,6,7,8-tetrahydro-2-(phenoxymethyl)-4H-thiazolo[5,4-c]azepin-4-one

Product 1

HCID 666093375,6,7,8-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-4H-thiazolo[5,4-c]azepin-4-oneYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 60% dispersion of sodium hydride in mineral oils (0.014 g, 0.36 mmol) was added to a stirred solution of 5,6,7,8-tetrahydro-2-(phenoxymethyl)-4H-thiazolo[5,4-c]azepin-4-one (0.066 g, 0.24 mmol) in DMF anhydrous (1 mL) at 0° C. and the mixture was stirred at room temperature for 1 hour. Then, benzyl bromide (0.043 mL, 0.36 mmol) was added and the mixture was stirred at room temperature for 16 hours. The mixture was diluted with H2O and extracted with DCM. The organic layer was separated, washed with brine, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 100/0). The desired fractions were collected and the solvents evaporated in vacuo to yield 5,6,7,8-tetrahydro-2-(phenoxymethyl)-5-(phenylmethyl)-4H-thiazolo[5,4-c]azepin-4-one (0.084 g, 96% yield) as a colourless oil. C21H20N2O2S LCMS: Rt 3.02, m/z 365 [M+H]+ (using method, LC-MS Method 6).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hours
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 100/0)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-76bfda4d7b614ca1817971ddb9a301c8
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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