Ammonium Chloride → HCID 70663230, compound

HRID 878269Notes

Reaction equation

HRID 878269 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:30])[C:15]([C:17]2[CH:18]=[C:19](B(O)O)[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=2)=[O:16])=[C:4]([O:31][CH3:32])[CH:3]=1.I[CH:34]1[CH2:37][O:36][CH2:35]1.Cl.N[C@@H]1CCCC[C@H]1O.C[Si](C)(C)N[Si](C)(C)C.[Na].[NH4+].[Cl-]>CC(O)C.[Ni](I)I.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:30])[C:15](=[O:16])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([CH:34]3[CH2:37][O:36][CH2:35]3)[CH:18]=2)=[C:4]([O:31][CH3:32])[CH:3]=1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 133566863-IodooxetaneHCID 45051731Sodium hexamethyidisilazaneHCID 70663648HCID 70663648, compound

Product 1

HCID 70663230HCID 70663230, compound

Reagents, catalysts & solvents 3

HCID 26038Nickel(II) iodideCatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 3-((4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylboronic acid (0.1 g, 223 μmol) in 2-propanol (1 mL) were added 3-iodooxetane (41.0 mg, 223 μmol), (1R,2R)-2-aminocyclohexanol hydrochloride (2.03 mg, 13.4 μmol), nickel(II) iodide (4.18 mg, 13.4 μmol) and sodium hexamethyldisilazan (40.9 mg, 223 μmol) and the suspension was heated in a microwave oven at 80° C. for 20 minutes. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). The mixture was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless solid (0.004 g; 3%). MS (ESI): m/z=461.15 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. additiontreated with silica gel
  6. customevaporated
  7. customThe compound was purified by silica gel chromatography on a 10 g column
  8. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
  9. customThe mixture was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-fa3f48499e6c4f2a94e8c7ec2640fa8c
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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