1-(Diphenylmethyl)azetidine-3-carbonitrile → HCID 58079830, compound

HRID 1258010Notes

Reaction equation

HRID 1258010 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])[CH:5]=[CH:4][C:3]=1F.[CH:16]([N:29]1[CH2:32][CH:31]([C:33]#[N:34])[CH2:30]1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH:16]([N:29]1[CH2:32][C:31]([C:3]2[CH:4]=[CH:5][C:6]([CH:8]([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])=[CH:7][C:2]=2[Br:1])([C:33]#[N:34])[CH2:30]1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 27792901-(Diphenylmethyl)azetidine-3-carbonitrileHCID 3251421Potassium bis(trimethylsilyl)amideHCID 131165852-Bromo-4-(diethoxymethyl)-1-fluorobenzene

Product 1

HCID 58079830HCID 58079830, compoundYield 75.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-4-(diethoxymethyl)-1-fluorobenzene (Preparation 15, 10.0 g, 36.0 mmol) in THF (125 mL) was added 1-benzhydrylazetidine-3-carbonitrile (13.4 g, 54.1 mmol) and KHMDS (10.8 g, 54.1 mmol). The reaction mixture is left stirring at room temperature for 1 hour. Next, the reaction mixture is concentrated to an oil under vacuum, diluted with EtOAc, and washed 2× with water. The organic phase was dried (Na2SO4) and concentrated under vacuum. The crude material was chromatographed (220 g Redi-Sep column) eluting from 100% heptane to 20:80 EtOAc:heptane to afford the intermediate (13.7 g, 75%) as a solid. 1HNMR (CDCl3) δ ppm: 7.73 (1H), 7.48-7.44 (5H), 7.37-23 (6H), 7.13 (1H), 5.47 (1H), 4.33 (1H), 4.14 (2H), 3.65-3.52 (4H), 3.41 (2H), 1.29-1.25 (6H).

Workup

  1. waitThe reaction mixture is left
  2. concentrationNext, the reaction mixture is concentrated to an oil under vacuum
  3. additiondiluted with EtOAc
  4. washwashed 2× with water
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. customThe crude material was chromatographed (220 g Redi-Sep column)
  8. washeluting from 100% heptane to 20:80 EtOAc

Sources & evidence

ORD record
ord-ce186ac0a3e446f28f20fbf873cdd7d3
Source dataset
uspto-grants-2013_06
Patent number
US08466115B2

Reaction notes

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