Dimethyl Sulfoxide → 3-(5-Bromo-2-formyl-phenoxy)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

HRID 237288Notes

Reaction equation

HRID 237288 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:16][C:17]1[CH:28]=[CH:27][C:20]([CH:21]=NC(C)(C)C)=[C:19](F)[CH:18]=1.CS(C)=[O:32]>O>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([O:13][C:27]2[CH:28]=[C:17]([Br:16])[CH:18]=[CH:19][C:20]=2[CH:21]=[O:32])([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydride2×HCID 54751705tert-Butyl 3-hydroxy-3-methylazetidine-1-carboxylate2×HCID 67343773(4-Bromo-2-fluoro-benzylidene)-tert-butyl-amine

Product 1

HCID 866570623-(5-Bromo-2-formyl-phenoxy)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of the title compound from Step B (400 mg, 2.2 mmol) in DMSO (8 mL) was added 60% NaH (120 mg, 3.0 mmol). After 30 min, the title compound from Step A was added and the resulting mixture was heated at 125° C. for 1 h in a microwave reactor. An additional quantity of the title compound from Step B (100 mg) and 60% NaH (32 mg) were added to the reaction. Heating was then resumed at 125° C. for another 1 h in a microwave reactor. The reaction was diluted with H2O and extracted with EtOAc (3×) followed by methanolic EtOAc (2×). The organics were dried, then THF (5 mL), H2O (5 mL) and AcOH (3 mL) were added. After 18 h at rt, the reaction was diluted with H2O and extracted with CH2Cl2. The organics were dried and purified by PTLC to give the title compound as an off white solid (247 mg, 31%). 1H NMR (CDCl3): 10.36 (s, 1H), 7.74 (d, J=8.3 Hz, 1H), 7.22-7.20 (m, 1H), 6.68 (d, J=1.6 Hz, 1H), 4.25 (d, J=9.2 Hz, 2H), 4.03 (d, J=9.8 Hz, 2H), 1.55 (s, 3H), 1.46 (m, 9H).

Workup

  1. temperatureHeating
  2. waitwas then resumed at 125° C. for another 1 h in a microwave reactor
  3. extractionextracted with EtOAc (3×)
  4. customThe organics were dried
  5. additionTHF (5 mL), H2O (5 mL) and AcOH (3 mL) were added
  6. waitAfter 18 h at rt
  7. additionthe reaction was diluted with H2O
  8. extractionextracted with CH2Cl2
  9. customThe organics were dried
  10. custompurified by PTLC

Sources & evidence

ORD record
ord-c0ba11d7c70b403c809282d0fab6f226
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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