Dimethylformamide → Methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate

HRID 658982Notes

Reaction equation

HRID 658982 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[C:17]#[C:18][Si](C)(C)C)[CH2:5][N:6]1[CH2:9][CH:8]([C:10]([O:12][CH3:13])=[O:11])[CH2:7]1.[F-].[Cs+].CN(C=O)C>CO>[C:17]([C:16]1[CH:15]=[CH:14][C:4]([CH2:5][N:6]2[CH2:9][CH:8]([C:10]([O:12][CH3:13])=[O:11])[CH2:7]2)=[CH:3][C:2]=1[F:1])#[CH:18]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 59651825Methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate

Product 1

HCID 25254788Methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate (20.9 g, 65 mmol) and cesium fluoride (11 g, 72 mmol) were added to DMF (50 mL). MeOH (100 mL) was added. After 2 h, MeOH was removed and the mixture was extracted with DCM and water. The organic layer was washed with brine and dried over magnesium sulfate. The solvent was removed and the material was purified by Biotage (75 L, 7-100% EtOAc/hexanes), affording methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate as light yellow oil. MS (ESI) m/z: Calculated: 247.1; Observed: 248.0 (M++1). 1-(4-(2-(5-Benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylic acid and 1-(4-(2-(5-Benzylpyridin-2-yl)ethyl)-3-fluorobenzyl)azetidine-3-carboxylic acid

Workup

  1. customMeOH was removed
  2. extractionthe mixture was extracted with DCM and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed
  6. customthe material was purified by Biotage (75 L, 7-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-088dd13effa64e9992b15407e4487e50
Source dataset
uspto-grants-2011_12
Patent number
US08080542B2

Reaction notes

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