N,N,N',N'-Tetramethylazodicarboxamide → 2-(4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-phenoxy)-2-methyl-propionic acid ethyl ester

HRID 417121Notes

Reaction equation

HRID 417121 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[CH2:28]([O:30][C:31](=[O:43])[C:32]([O:35][C:36]1[CH:41]=[CH:40][C:39](O)=[CH:38][CH:37]=1)([CH3:34])[CH3:33])[CH3:29].C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[CH2:28]([O:30][C:31](=[O:43])[C:32]([O:35][C:36]1[CH:41]=[CH:40][C:39]([O:15][CH2:14][CH:13]([N:12]2[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=[C:8]2[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[CH:38][CH:37]=1)([CH3:34])[CH3:33])[CH3:29]

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 181741Ethyl 2-(4-hydroxyphenoxy)-2-methylpropanoateHCID 666193102-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol

Product 1

HCID 666195062-(4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-phenoxy)-2-methyl-propionic acid ethyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 200 mg (0.512 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c) in 5 ml tetrahydrofuran were added 126 mg (0.563 mmol) 2-(4-hydroxy-phenoxy)-2-methyl-propionic acid ethyl ester (CAS RN 42806-90-6) and 124 mg (0.614 mmol) tri-n-butylphosphin. The reaction mixture was cooled down to 0° C. 106 mg (0.614 mmol) N,N,N′,N′-tetramethylazodicarboxamide were added and the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was concentrated under vacuum and the residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30) to give the title compound as colorless solid (74%). MS (Turbo Spray): m/z=597.2 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30)

Sources & evidence

ORD record
ord-17c1857e232c4267818c1fb9b1a43362
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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