Dimethylformamide → Tert-butyl 3-fluoro-3-(4-formylphenyl)azetidine-1-carboxylate

HRID 1961526Notes

Reaction equation

HRID 1961526 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)([F:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.CN([CH:28]=[O:29])C.[NH4+].[Cl-]>C1COCC1>[F:12][C:10]1([C:13]2[CH:18]=[CH:17][C:16]([CH:28]=[O:29])=[CH:15][CH:14]=2)[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 58079744Tert-butyl 3-(4-bromophenyl)-3-fluoroazetidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 58079777Tert-butyl 3-fluoro-3-(4-formylphenyl)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-3-(4-bromophenyl)-3-fluoroazetidine-1-carboxylate (Preparation 5, 1.0 g, 3 mmol) in THF (10 mL) at −78° C. was slowly added n-BuLi (2.1 mL of 1.6M solution in hexanes). The reaction was stirred at −78° C. for 15 minutes at which time DMF (0.5 mL, 6 mmol) was added. Reaction mixture was allowed to warm to room temperature and stir for additional 1 hour. Saturated aqueous NH4Cl (10 mL) was added and the aqueous phase was extracted with ether (2×10 mL). The combined organic phases were dried (Na2SO4) and concentrated under vacuum. Crude product was chromatographed on silica (12 g column) using a gradient of 0-30% EtOAc/hexanes in a 12 minute run. Yield 460 mg. LC/MS retention time=3.004 minutes; MS calculated for (C15H18FNO3), 279.127; found 180.2 M-BOC. 1H NMR (CDCl3) δ 10.0 (s, 1H), 8.0 (d, 2H), 7.7 (d, 2H), 4.5 (m, 2H), 4.2 (m, 2H), 1.6 (s, 9H).

Workup

  1. customat −78° C.
  2. additionwas added
  3. customReaction mixture
  4. extractionthe aqueous phase was extracted with ether (2×10 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. customCrude product was chromatographed on silica (12 g column)
  8. customin a 12 minute

Sources & evidence

ORD record
ord-2a25f310c11244aea1b3f4c45ae6f56f
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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