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

HRID 2038455Notes

Reaction equation

HRID 2038455 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)[CH:16]=[CH:15][C:14]=2[CH:20]=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[CH3:22])[CH:16]=[CH:15][C:14]=2[CH:20]=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 27332672-Methylphenyl boronic acidHCID 866570483-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866570473-(4-Formyl-2'-methyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl esterYield 99.1%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

To 3-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (1.4 g, 3.9 mmol), 2-methylphenylboronic acid (0.55 g, 4.1 mmol), K3PO4 (2.5 g, 11.7 mmol), Pd(dba)2 (0.046 g, 0.080 mmol) and QPhos (0.114 g, 0.160 mmol) was added PhCH3 (16 mL). After 18 h at rt the reaction was diluted with EtOAc and filtered through a small silica pad. Silica gel chromatography (10-40% EtOAc in hexanes) gave 1.42 g (98% yield) of the title compound. 1H NMR (CDCl3): 7.26-7.18 (m, 4H), 6.94 (d, J=8.3 Hz, 1H), 6.90 (dd, J=8.2, 2.0 Hz, 1H), 6.55 (d, J=1.9 Hz, 1H), 4.90-4.86 (m, 1H), 4.26 (dd, J=10.1, 6.3 Hz, 2H), 4.12 (m, 4H), 2.26 (s, 3H), 1.49 (t, J=7.0 Hz, 3H), 1.44 (s, 9H).

Workup

  1. filtrationfiltered through a small silica pad

Sources & evidence

ORD record
ord-7459ccd20c89496783a416df7424fdf8
Source dataset
uspto-grants-2013_11
Patent number
US08575364B2

Reaction notes

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