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

HRID 1850089Notes

Reaction equation

HRID 1850089 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].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>CCOC(C)=O.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:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[C:23]([F:34])([F:33])[F:22])[CH:16]=[CH:15][C:14]=2[CH:20]=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 866570483-(5-Bromo-2-formyl-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 873639173-(4-Formyl-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl esterYield 101.7%

Reagents, catalysts & solvents 2

HCID 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 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).

Workup

  1. filtrationfiltered through a small silica pad

Sources & evidence

ORD record
ord-8bae8d0bca6b472d9f3634ea927f6b44
Source dataset
uspto-grants-2015_02
Patent number
US08957059B2

Reaction notes

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