Toluene → 3-(4-Formyl-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

https://huagongshe.com/reaction/2038457

Participants

Role	Name	HCID	Charge
Reactant	Toluene	HCID 1140	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	2-(Trifluoromethyl)benzeneboronic acid	HCID 2734387	—
Reactant	3-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester	HCID 86657048	—
Catalyst	Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene	HCID 129828017	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	3-(4-Formyl-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester	HCID 87363917	101.7%

Reaction Steps

To the title compound of Example 1 Step B (0.20 g, 0.56 mmol), 2-trifluoromethylphenylboronic acid (0.16 g, 0.84 mmol), K3PO4 (0.357 g, 1.68 mmol) Pd(dba)2 (0.013 g, 0.022 mmol) and Q-Phos (0.008 g, 0.011 mmol) was added PhCH3. After 48 h at rt the reaction was diluted with EtOAc and filtered through a small silica pad. Silica gel chromatography (0-30% EtOAc in hexanes) gave 0.24 g (99% yield) of the title compound. MS (ESI): mass calcd. for C22H22F3NO4, 421.15; m/z found, 336.1 [M-56]+, 444.1 [M+Na]+. 1H NMR (CDCl3): 10.53 (d, J=0.7 Hz, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.3 Hz, 1H), 7.54 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.5 Hz, 1H), 7.05 (d, J=7.9 Hz, 1H), 6.59 (s, 1H), 4.99 (tt, J=6.4, 4.0 Hz, 1H), 4.37-4.29 (m, 2H), 4.11-4.08 (m, 2H), 1.45 (s, 9H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08575364B2
Source dataset	uspto-grants-2013_11
ORD ID	ord-314cb63655234b8f8c24bdd52f067b2a
Source note	uspto-grants-2013_11