Imidazole → 9-Bromo-3-(tert-butyldimethylsilyloxy)-2,3,4,5-tetrahydrobenzo-[b][1,4]oxazepine

HRID 2175304Notes

Reaction equation

HRID 2175304 reaction equation
[Br:1][C:2]1[C:7]2[O:8][CH2:9][CH:10]([OH:13])[CH2:11][NH:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[CH3:19][C:20]([Si:23](Cl)([CH3:25])[CH3:24])([CH3:22])[CH3:21]>CN(C=O)C.C(=O)(O)[O-].[Na+]>[Br:1][C:2]1[C:7]2[O:8][CH2:9][CH:10]([O:13][Si:23]([C:20]([CH3:22])([CH3:21])[CH3:19])([CH3:25])[CH3:24])[CH2:11][NH:12][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 867126039-Bromo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ol

Product 1

HCID 867126049-Bromo-3-(tert-butyldimethylsilyloxy)-2,3,4,5-tetrahydrobenzo-[b][1,4]oxazepineYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 9-bromo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ol (0.456 g, 1.868 mmol) and imidazole (0.280 g, 4.11 mmol) in DMF (5.0 mL) was added TBSCl (0.619 g, 4.11 mmol). The reaction was stirred at room temperature for 18 h. The mixture was diluted with a solution of saturated sodium bicarbonate (15 ml) and extracted with ethyl acetate (20 mL). The organic layer was dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (0-50% ethyl acetate:hexanes) to afford the title compound (648 mg, 1.718 mmol, 92% yield) as clear oil. LCMS, [M+H]+=360.1. 1H NMR (400 MHz, CDCl3) δ 6.99 (dd, J=7.8, 1.4 Hz, 1H), 6.69 (t, J=7.9 Hz, 1H), 6.57 (dd, J=7.9, 1.5 Hz, 1H), 4.39 (dd, J=11.9, 4.8 Hz, 1H), 4.19 (tt, J=6.5, 4.7 Hz, 1H), 3.94 (dd, J=11.9, 6.8 Hz, 1H), 3.67 (br. s., 1H), 3.54 (dt, J=13.2, 4.1 Hz, 1H), 3.17 (dd, J=12.3, 5.5 Hz, 1H), 0.93-0.90 (m, 9H), 0.11 (s, 6H).

Workup

  1. extractionextracted with ethyl acetate (20 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0-50% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-bc02f626a7c944569bdb3181cce97cab
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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