Water → tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl(methyl)carbamate

HRID 1915779Notes

Reaction equation

HRID 1915779 reaction equation
[F:1][C:2]1([F:26])[CH2:8][N:7]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:6][CH2:5][CH:4]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:3]1.[CH3:27][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC.O>C1COCC1>[F:26][C:2]1([F:1])[CH2:8][N:7]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:6][CH2:5][CH:4]([N:18]([CH3:27])[C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 86679991tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate

Product 1

HCID 86679990tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl(methyl)carbamateYield 90.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (ice-water bath) solution of tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate (190 mg, 0.51 mmol) in THF (10 mL) was added lithium hexamethyldisilazide (1M in THF, 0.8 mL, 0.8 mmol) and the mixture stirred for 30 min. Iodomethane (0.06 mL, 1.02 mmol) was added and the mixture stirred at room temperature for 16 hr. Water (2 mL) was added and the mixture extracted with EtOAc (30 mL). The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-70% EtOAc/isohexane) gave tert-butyl 6,6-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl(methyl)carbamate (180 mg, 90%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.09-7.99 (m, 1H), 4.57-4.38 (m, 1H), 3.85 (s, 3H), 3.84-3.53 (m, 1H), 3.45-3.15 (m, 3H), 2.81 (s, 3H), 2.53-2.29 (m, 2H), 2.16-2.01 (m, 2H), 1.48 (s, 9H).

Workup

  1. stirringthe mixture stirred at room temperature for 16 hr
  2. extractionthe mixture extracted with EtOAc (30 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customthe solvent removed under reduced pressure
  6. customPurification via silica gel column chromatography (0-70% EtOAc/isohexane)

Sources & evidence

ORD record
ord-eb18784043184a87a4fa54d109b599f5
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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