Formaldehyde → HCID 89639167, compound

HRID 1500806Notes

Reaction equation

HRID 1500806 reaction equation
C[Mg]Br.Br[C:5]1[CH:6]=[C:7]([C:18]#[N:19])[N:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:9]=1.C([Li])CCC.CCCCCC.[CH2:31]=[O:32]>C1COCC1>[C:13]([O:12][C:11](=[O:17])[NH:10][N:8]1[CH:9]=[C:5]([CH2:31][OH:32])[CH:6]=[C:7]1[C:18]#[N:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 8058HexaneHCID 57955231tert-Butyl (4-bromo-2-cyano-1H-pyrrol-1-yl)carbamateHCID 178418339ButyllithiumHCID 178418573HCID 178418573, compound

Product 1

HCID 89639167HCID 89639167, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-60 °C

Procedure

Under argon, a 1 M solution of methylmagnesium bromide in THF (13.3 ml) was added over 15 min to a solution of tert-butyl (4-bromo-2-cyano-1H-pyrrol-1-yl)carbamate (3.7 g, 12.09 mmol; preparation described in PCT Int. Pat. Appl. WO 2007/064883, Intermediate AAE, Step 3) in THF (37 ml) cooled to −60° C. After 30 min, a 1.6 M solution of n-butyllithium in hexane (15.1 ml, 24.2 mmol) was added over 10 min to the reaction, and the resulting mixture was stirred between −60° C. and −40° C. for 1 h. Then, paraformaldehyde (1.09 g, 36.3 mmol) was added to the reaction, and the reaction mixture was slowly warmed to rt and stirred overnight. After quenching with sat. aq. ammonium chloride solution, the aqueous layer was extracted twice with ethyl acetate. The combined organic phases were washed with sat. aq. sodium chloride solution, dried over sodium sulfate and evaporated. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate 2:1→1:1) afforded 2.04 g (69% of th.) of the title compound.

Workup

  1. temperaturethe reaction mixture was slowly warmed to rt
  2. stirringstirred overnight
  3. customAfter quenching with sat. aq. ammonium chloride solution
  4. extractionthe aqueous layer was extracted twice with ethyl acetate
  5. washThe combined organic phases were washed with sat. aq. sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customPurification by column chromatography on silica gel (cyclohexane/ethyl acetate 2:1→1:1)

Sources & evidence

ORD record
ord-bac3091111d64cb0a68d9d5d50314bc8
Source dataset
uspto-grants-2015_12
Patent number
US09206184B2

Reaction notes

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