Methyl iodide → Tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2,5-dimethylphenyl)carbamate

HRID 1771741Notes

Reaction equation

HRID 1771741 reaction equation
[CH3:1]C1(C)CCCC(C)(C)N1.[Li]C(CC)C.[C:16]([O:20][C:21]([N:23]([C:31]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([Br:38])[C:32]=1[CH3:39])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:22])([CH3:19])([CH3:18])[CH3:17].IC.[NH4+].[Cl-]>C1COCC1>[C:16]([O:20][C:21]([N:23]([C:31]1[C:36]([F:37])=[C:35]([CH3:1])[CH:34]=[C:33]([Br:38])[C:32]=1[CH3:39])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:22])([CH3:17])([CH3:18])[CH3:19]

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 89443893tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2-methylphenyl)carbamateHCID 178418400CID 53628100

Product 1

HCID 89443814Tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2,5-dimethylphenyl)carbamateYield 85.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

To a stirred solution of 2,2,6,6-tetramethylpiperidine (699 mg, 4.9 mmol, 2.0 eq) in THF (7.5 mL) at −50° C. was added sec-BuLi (3.8 mL, 1.3 M, 4.9 mmol, 2.0 eq) dropwise. The reaction was stirred for 20 min at −15° C. to −10° C., then cooled to −65° C. and a solution of tert-butyl N-tert-butoxycarbonyl-N-(3-bromo-6-fluoro-2-methylphenyl)carbamate (See example 13) (1 g, 2.47 mmol, 1.0 eq) in THF (7.5 mL) added dropwise. The reaction was stirred a further 2 h at −65° C. Iodomethane (1.05 g, 7.41 mmol, 3.0 eq) was added in one portion and the reaction allowed to warm to −10° C. over 30 min. The reaction was then poured into saturated aqueous NH4Cl and extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4) filtered and evaporated in vacuo to give a crude residue, which was purified by column chromatography (petroleum ether:EtOAc, 100:0 to 30:1) to give the title compound as a white solid (880 mg, 85%).

Workup

  1. stirringThe reaction was stirred a further 2 h at −65° C
  2. temperatureto warm to −10° C. over 30 min
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give a crude residue, which
  9. customwas purified by column chromatography (petroleum ether:EtOAc, 100:0 to 30:1)

Sources & evidence

ORD record
ord-a909f17a9c0742debcd54d060875ca6a
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

Loading…