3-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester → 3-[5-Bromo-2-(hydroxy-phenyl-methyl)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester

HRID 237310Notes

Reaction equation

HRID 237310 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=2[CH:20]=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]1([Mg]Br)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=2[CH:20]([OH:21])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 866570483-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl esterHCID 178418255HCID 178418255, compound

Product 1

HCID 673464273-[5-Bromo-2-(hydroxy-phenyl-methyl)-phenoxy]-azetidine-1-carboxylic acid tert-butyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(5-bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.70 mmol) in CH2Cl2 (10 mL) was added a solution of PhMgBr (1M in THF, 1 mL). The reaction was allowed to stir for 15 h then quenched with 1N HCl (4 mL). After 10 min, the mixture was made basic with 1N NaOH (10 mL), and extracted with CH2Cl2 (3×20 mL). The organic layers were combined and dried. Chromatography of the resulting residue (SiO2; EtOAc/Hexanes) gave the title compound (0.24 g, 79%). MS (ESI): mass calcd. for C21H24BrNO4, 433.1; m/z found, 434.4 [M+H]+. 1H NMR (CDCl3): 7.41-7.23 (m, 6H), 7.17 (dd, J=8.2, 1.7, 1H), 6.61 (d, J=1.7, 1H), 6.04 (s, 1H), 4.90-4.68 (m, 1H), 4.32-4.01 (m, 2H), 3.95-3.68 (m, 2H), 2.04-2.10, 1H), 1.44 (s, 9H).

Workup

  1. customthen quenched with 1N HCl (4 mL)
  2. waitAfter 10 min
  3. extractionextracted with CH2Cl2 (3×20 mL)
  4. customdried

Sources & evidence

ORD record
ord-ad5209b0fc0e41f381197007e76f5785
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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