Sodium Iodide → 3-(2-{[4-Chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

HRID 1486000Notes

Reaction equation

HRID 1486000 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]([CH3:21])[C:9]2[CH:20]=[CH:19][CH:18]=[CH:17][C:10]=2[O:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[O:7])=[CH:4][C:3]=1[C:24]1[CH:25]=[N:26][C:27]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:29]=1[C:30]#[N:31].[CH:36]1([O:42][C:43](=[O:48])[O:44][CH:45](Cl)[CH3:46])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.C(N(CC)CC)C.[Na+].[I-]>CN(C=O)C.C(OCC)(=O)C>[CH:36]1([O:42][C:43]([O:44][CH:45]([O:15][C:14](=[O:16])[CH2:13][CH2:12][O:11][C:10]2[CH:17]=[CH:18][CH:19]=[CH:20][C:9]=2[N:8]([C:6](=[O:7])[C:5]2[CH:22]=[CH:23][C:2]([Cl:1])=[C:3]([C:24]3[CH:25]=[N:26][C:27]([C:32]([F:35])([F:33])[F:34])=[CH:28][C:29]=3[C:30]#[N:31])[CH:4]=2)[CH3:21])[CH3:46])=[O:48])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 112295291-Chloroethyl Cyclohexyl CarbonateHCID 251587413-(2-{[4-Chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid

Product 1

HCID 593703313-(2-{[4-Chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid 11-4 (500 mg, 0.95 mmol), carbonic acid 1-chloroethyl cyclohexyl ester (393 mg, 1.9 mmol), triethylamine (399 μL, 2.85 mmol), and NaI (142.5 mg, 0.95 mmol) in DMF (5 mL) were stirred at 60° C. for 1 day. Ethyl acetate was added and the mixture was washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with 20% ethyl acetate in hexane to afford 3-(2-{[4-Chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionic acid 1-cyclohexyloxycarbonyloxy-ethyl ester 37-1. MS [M+H]+: 674.2; tR=35.7 min (method 5).

Workup

  1. washthe mixture was washed with water and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel flash column chromatography
  6. washeluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9d9fabb2b38d48798015beb885f278f4
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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