Methyl iodide → tert-butyl [(3S)-1,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate

HRID 1670422Notes

Reaction equation

HRID 1670422 reaction equation
[H-].[Na+].[CH3:3][N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[NH:8][C:7](=[O:15])[C@@H:6]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:5]1.[CH3:24]I>C1COCC1>[CH3:24][N:8]1[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:4]([CH3:3])[CH2:5][C@H:6]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[C:7]1=[O:15]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57617722tert-butyl ((S)-1-methyl-4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl)carbamate

Product 1

HCID 57617768tert-butyl [(3S)-1,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamateYield 115.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

36 mg of sodium hydride in suspension at 60% in oil (0.90 mmol) are introduced at −10° C. into a 50 mL round-bottomed flask, with stirring and under an argon atmosphere, containing 10 mL of THF and 265 mg of 11 (0.91 mmol). The medium is stirred for 1 h, and then 148 mg (1.04 mmol) of methyl iodide are added. The medium is kept stirring at RT for 24 h. The mixture is concentrated, and 320 mg of crude product are obtained, which product is chromatographed on a silica cartridge (50 g, eluent heptane/AcOEt—in an AcOEt gradient: 10 to 50%). 235 mg of expected product 17 are recovered.

Workup

  1. stirringThe medium is stirred for 1 h
  2. stirringThe medium is kept stirring at RT for 24 h
  3. concentrationThe mixture is concentrated

Sources & evidence

ORD record
ord-1a20521274b34d4d8acd53f44a70952b
Source dataset
uspto-grants-2011_08
Patent number
US07994161B2

Reaction notes

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