Water → HCID 66993408, compound

HRID 2188676Notes

Reaction equation

HRID 2188676 reaction equation
[CH3:1][CH:2]([NH:4][C:5]1[CH:22]=[N:21][C:8]2[CH2:9][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:12][O:13][C:7]=2[N:6]=1)[CH3:3].C[Si](C)(C)[N-][Si](C)(C)C.[K+].I[CH2:34][CH3:35].O>O1CCCC1>[CH2:34]([N:4]([CH:2]([CH3:1])[CH3:3])[C:5]1[CH:22]=[N:21][C:8]2[CH2:9][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:12][O:13][C:7]=2[N:6]=1)[CH3:35]

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66993578HCID 66993578, compound

Product 1

HCID 66993408HCID 66993408, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 3-[(1-methylethyl)amino]-6,7-dihydropyrazino[2,3-f][1,4]oxazepine-8(9H)-carboxylate (137 mg) in tetrahydrofuran (3 mL) was added dropwise potassium hexamethyl disilazide (1.06 mL, 0.5 M toluene solution) at 0° C. The mixture was stirred at 0° C. for 15 min, and iodoethane (105 μL) was added dropwise thereto. The mixture was stirred at 0° C. for 1.5 hr, and further at room temperature overnight. Water (5 mL) was added, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient: 10→40% ethyl acetate/hexane) to give the title compound (10 mg, 7%) as a pale-yellow oil.

Workup

  1. stirringThe mixture was stirred at 0° C. for 1.5 hr
  2. customfurther at room temperature
  3. customovernight
  4. extractionthe mixture was extracted with ethyl acetate
  5. extractionThe aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layer was washed with water and saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (solvent gradient: 10→40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-eaeebbf2323f40e38918c3354009f923
Source dataset
uspto-grants-2012_12
Patent number
US08324201B2

Reaction notes

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