4-Fluorobenzaldehyde → HCID 57659776, compound

HRID 1011618Notes

Reaction equation

HRID 1011618 reaction equation
C([Mg]Cl)(C)C.[Li]CCCC.I[C:12]1[C:16]([CH2:17][N:18]([S:26]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][N:14]([CH2:39][O:40][CH3:41])[N:13]=1.[F:42][C:43]1[CH:50]=[CH:49][C:46]([CH:47]=[O:48])=[CH:45][CH:44]=1>C1COCC1>[F:42][C:43]1[CH:50]=[CH:49][C:46]([CH:47]([OH:48])[C:12]2[C:16]([CH2:17][N:18]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][N:14]([CH2:39][O:40][CH3:41])[N:13]=2)=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 680234-FluorobenzaldehydeHCID 57659751HCID 57659751, compoundHCID 178418339ButyllithiumHCID 178418918HCID 178418918, compound

Product 1

HCID 57659776HCID 57659776, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a flame-dried flask under nitrogen was added THF (3 mL) followed by isopropylmagnesium chloride (2M THF, 0.708 mL) and the mixture cooled to −10° C. n-BuLi (1.6M Hexane, 1.77 mL) was added dropwise and stirred for 30 minutes. The reaction was cooled to −78° C. and tert-butyl (3-iodo-1-(methoxymethyl)-1H-pyrazol-4-yl)methyl(4-(trifluoromethyl)phenylsulfonyl)carbamate (43) (815 mg, 1.42 mmol) in THF (3 mL) was added dropwise and stirred for 30 minutes. 4-Fluorobenzaldehyde (0.91 mL, 8.52 mmol) was added neat and stirred for 1 hr before quenching with aq. ammonium chloride (5 mL). The aqueous layer was discarded and the reaction was concentrated in vacuo. The resulting crude product was purified by column chromatography using EtOAc/hexane gradients to yield tert-butyl (3-((4-fluorophenyl)(hydroxy)methyl)-1-(methoxymethyl)-1H-pyrazol-4-yl)methyl(4-(trifluoromethyl)phenylsulfonyl)carbamate (44) (447 mg, 55%) as a clear oil.

Workup

  1. additionwas added dropwise
  2. stirringstirred for 30 minutes
  3. stirringstirred for 1 hr
  4. custombefore quenching with aq. ammonium chloride (5 mL)
  5. concentrationthe reaction was concentrated in vacuo
  6. customThe resulting crude product was purified by column chromatography

Sources & evidence

ORD record
ord-8eb9d4d1bed64956ba01de5e23e9f824
Source dataset
uspto-grants-2011_07
Patent number
US07977368B2

Reaction notes

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