Sodium hydride → HCID 71237763, compound

HRID 2038730Notes

Reaction equation

HRID 2038730 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[N:15]=[C:16]([I:18])[NH:17][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:21][Si:22]([CH2:25][CH2:26][O:27][CH2:28]Cl)([CH3:24])[CH3:23]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[N:15]=[C:16]([I:18])[N:17]([CH2:28][O:27][CH2:26][CH2:25][Si:22]([CH3:24])([CH3:23])[CH3:21])[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 71237842HCID 71237842, compound

Product 1

HCID 71237763HCID 71237763, compoundYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-iodo-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine-6-carboxylic acid tert-butyl ester (Preparation 28, 2.2 g, 6.06 mmol) in THF (35 mL) was added NaH (60% in paraffin oil, 254 mg, 6.36 mmol) and the resulting solution was stirred at room temperature for 1.5 hours. The reaction mixture was cooled to 0° C. and SEM-Cl (1.13 mL, 6.36 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 18 hours and then cooled to 0° C. and quenched carefully with water (100 mL). The resulting solution was extracted with EtOAc (2×100 mL) and the combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (Biotage SNAP 100 g) eluting with 40% EtOAc in DCM to give the title compound (2.34 g) in a 78% yield.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. temperaturecooled to 0° C.
  4. customquenched carefully with water (100 mL)
  5. extractionThe resulting solution was extracted with EtOAc (2×100 mL)
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (Biotage SNAP 100 g)
  9. washeluting with 40% EtOAc in DCM

Sources & evidence

ORD record
ord-46ba19d59fea4968a4f8cc97f2be5073
Source dataset
uspto-grants-2013_11
Patent number
US08575336B2

Reaction notes

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