4-Fluorobenzyl bromide → Methyl 3-(diphenylmethyleneamino)-1-(4-fluorobenzyl)cyclohexanecarboxylate

HRID 530873Notes

Reaction equation

HRID 530873 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]1([C:17](=[N:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH:27]([C:31]([O:33][CH3:34])=[O:32])[CH2:26]2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[F:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40]Br)=[CH:38][CH:37]=1>O1CCCC1>[C:11]1([C:17](=[N:24][CH:25]2[CH2:30][CH2:29][CH2:28][C:27]([CH2:40][C:39]3[CH:42]=[CH:43][C:36]([F:35])=[CH:37][CH:38]=3)([C:31]([O:33][CH3:34])=[O:32])[CH2:26]2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 680214-Fluorobenzyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86698247Methyl 3-(diphenylmethyleneamino)cyclohexanecarboxylate

Product 1

HCID 86698248Methyl 3-(diphenylmethyleneamino)-1-(4-fluorobenzyl)cyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

In a flask, lithium bis(trimethylsilyl)amide (LHMDS) (1M) in THF (2.83 mL, 2.83 mmol) was added to tetrahydrofuran (10 mL). The reaction mixture was cooled to −78° C., and then a solution of methyl 3-(diphenylmethyleneamino)cyclohexanecarboxylate (700 mg, 2.18 mmol) and tetrahydrofuran (1 mL) was added drop-wise to the reaction mixture at −78° C. The reaction was stirred at −78° C. for 30 minutes. Afterwards, 4-fluorobenzylbromide (0.402 mL, 3.27 mmol) was added, and the reaction was stirred for an additional 24 hours at 0° C. Upon reaction completion, the reaction was quenched with saturated ammonium chloride solution (50 mL) and extracted three times with ethyl acetate (50 mL). The organic layers were combined, dried with sodium sulfate, and concentrated to yield crude product. The crude product was progressed to the next step without further purification.

Workup

  1. stirringthe reaction was stirred for an additional 24 hours at 0° C
  2. customUpon reaction completion
  3. customthe reaction was quenched with saturated ammonium chloride solution (50 mL)
  4. extractionextracted three times with ethyl acetate (50 mL)
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customto yield crude product
  8. customThe crude product was progressed to the next step without further purification

Sources & evidence

ORD record
ord-03582d30a1274e539c3aeb07eb56bc2e
Source dataset
uspto-grants-2016_05
Patent number
US09351965B2

Reaction notes

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