2-(Di-tert-butylphosphino)biphenyl → (1-{4-[3-(4-Cyclopropylmethoxy-phenoxy)-azetidin-1-yl]-phenyl}-ethyl)-carbamic acid tert-butyl ester

HRID 40508Notes

Reaction equation

[CH:1]1([CH2:4][O:5][C:6]2[CH:16]=[CH:15][C:9]([O:10][CH:11]3[CH2:14][NH:13][CH2:12]3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[C:17]([O:21][C:22](=[O:33])[NH:23][C@H:24]([C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1)[CH3:25])([CH3:20])([CH3:19])[CH3:18].CC([O-])(C)C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>O1CCOCC1>[C:17]([O:21][C:22](=[O:33])[NH:23][CH:24]([C:26]1[CH:27]=[CH:28][C:29]([N:13]2[CH2:12][CH:11]([O:10][C:9]3[CH:15]=[CH:16][C:6]([O:5][CH2:4][CH:1]4[CH2:2][CH2:3]4)=[CH:7][CH:8]=3)[CH2:14]2)=[CH:30][CH:31]=1)[CH3:25])([CH3:18])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 45 °C

Procedure

To 0.9 g (4.1 mmol) 3-(4-cyclopropylmethoxy-phenoxy)-azetidine (IX.1), 1.2 g (4.1 mmol) (S)-[1-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (I.3), 1.6 g (16.4 mmol) NaOtBu, 0.49 g (1.64 mmol) 2-(di-tert-butylphosphino)biphenyl and 0.38 g (0.41 mmol) tris-(dibenzylideneacetone)-dipalladium(0) are added under an argon atmosphere 25 mL 1,4-dioxane. The mixture is stirred for 12 h at 45° C. The mixture is filtered, washed with MeOH and concentrated. The residue is purified by HPLC (silica gel; PE/ethyl acetate; gradient 9:1→1:1) to yield the desired product.

Workup

filtrationThe mixture is filtered
washwashed with MeOH
concentrationconcentrated
customThe residue is purified by HPLC (silica gel; PE/ethyl acetate; gradient 9:1→1:1)

Sources & evidence

ORD record: ord-43dd1fb6b8df4c818bac9889d4be644f
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530461B2

Reaction notes

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