2-(Di-tert-butylphosphino)biphenyl → N-(1-{4-[3-(4-Cyclopropylmethoxy-phenoxy)-azetidin-1-yl]-phenyl}-1-methyl-ethyl)-acetamide

HRID 40530Notes

Reaction equation

HRID 40530 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.Br[C:18]1[CH:23]=[CH:22][C:21]([C:24]([NH:27][C:28](=[O:30])[CH3:29])([CH3:26])[CH3:25])=[CH:20][CH:19]=1.CC([O-])(C)C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[CH:16]=[CH:15][C:9]([O:10][CH:11]3[CH2:12][N:13]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([NH:27][C:28](=[O:30])[CH3:29])([CH3:26])[CH3:25])=[CH:20][CH:19]=4)[CH2:14]3)=[CH:8][CH:7]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 39616691N-(2-(4-Bromophenyl)propan-2-YL)acetamideHCID 866890093-(4-Cyclopropylmethoxy-phenoxy)-azetidine

Product 1

HCID 86689031N-(1-{4-[3-(4-Cyclopropylmethoxy-phenoxy)-azetidin-1-yl]-phenyl}-1-methyl-ethyl)-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To 35 mg (0.16 mmol) 3-(4-cyclopropylmethoxy-phenoxy)-azetidine (IX.1) in THF (2.0 mL) are added under an argon atmosphere 41 mg (0.16 mmol) N-[1-(4-bromo-phenyl)-1-methyl-ethyl]-acetamide, 63 mg (0.64 mmol) NaOtBu, 19 mg (0.064 mmol) 2-(di-tert-butylphosphino)biphenyl and 15 mg (0.016 mmol) tris-(dibenzylidene-acetone)-dipalladium(0). The mixture is stirred for 12 h at 45° C. The mixture is filtered and concentrated in vacuo. The residue is purified by HPLC (Zorbax, acetronitrile/H2O (+0.15% HCOOH)) to yield the desired product.

Workup

  1. filtrationThe mixture is filtered
  2. concentrationconcentrated in vacuo
  3. customThe residue is purified by HPLC (Zorbax, acetronitrile/H2O (+0.15% HCOOH))

Sources & evidence

ORD record
ord-c0ff54126222457692099719ec6d4305
Source dataset
uspto-grants-2013_09
Patent number
US08530461B2

Reaction notes

Loading…