2-(Di-tert-butylphosphino)biphenyl → (S)-1-{4-[3-(4-Ethoxy-phenoxy)-azetidin-1-yl]-phenyl}-ethylamine

HRID 40507Notes

Reaction equation

[CH2:1]([O:3][C:4]1[CH:14]=[CH:13][C:7]([O:8][CH:9]2[CH2:12][NH:11][CH2:10]2)=[CH:6][CH:5]=1)[CH3:2].C(OC(=O)[NH:21][C@H:22]([C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)[CH3:23])(C)(C)C.CC([O-])(C)C.[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>O1CCOCC1.O.CO>[CH2:1]([O:3][C:4]1[CH:14]=[CH:13][C:7]([O:8][CH:9]2[CH2:12][N:11]([C:27]3[CH:28]=[CH:29][C:24]([C@@H:22]([NH2:21])[CH3:23])=[CH:25][CH:26]=3)[CH2:10]2)=[CH:6][CH:5]=1)[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

To 5.0 g (21.8 mmol) 3-(4-ethoxy-phenoxy)-azetidine and 6.5 g (21.8 mmol) (S)-[1-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (1.3) in 80 mL 1,4-dioxane under an argon atmosphere are added 8.6 g (87.1 mmol) KOtBu, 0.65 g (2.18 mmol) 2-(di-tert-butylphosphino)biphenyl and 1.0 g (1.09 mmol) tris-(dibenzylideneacetone)-dipalladium(0). The mixture is stirred for 2 h at 120° C. Subsequently 200 mL MeOH and 5 mL water are added and the mixture is filtered and concentrated in vacuo. The residue is taken up in ethyl acetate and is washed with water. The organic layer is concentrated and the residue is purified by HPLC (eluent A: water+0.1% NH4OH, eluent B: MeOH) to yield the desired product.

Workup

filtrationthe mixture is filtered
concentrationconcentrated in vacuo
washis washed with water
concentrationThe organic layer is concentrated
customthe residue is purified by HPLC (eluent A: water+0.1% NH4OH, eluent B: MeOH)

Sources & evidence

ORD record: ord-fdb4a14c01f14561a6767d063c044631
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530461B2

Reaction notes

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