Methoxymethyl-triphenylphosphonium chloride → Methyl 6-amino-4-(4-fluorophenyl)-2-(1-methylethyl)-5-(2-methoxyethenyl)nicotinate

HRID 29086Notes

Reaction equation

HRID 29086 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[NH2:30][C:31]1[N:36]=[C:35]([CH:37]([CH3:39])[CH3:38])[C:34]([C:40]([O:42][CH3:43])=[O:41])=[C:33]([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[C:32]=1[CH:51]=O>O1CCCC1.C(OCC)(=O)C>[NH2:30][C:31]1[C:32]([CH:51]=[CH:2][O:3][CH3:4])=[C:33]([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[C:34]([C:40]([O:42][CH3:43])=[O:41])=[C:35]([CH:37]([CH3:39])[CH3:38])[N:36]=1

Participants

6

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 11438468HCID 11438468, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 69311814Methyl 6-amino-4-(4-fluorophenyl)-2-(1-methylethyl)-5-(2-methoxyethenyl)nicotinate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (methoxymethyl)triphenyl-phosphonium chloride (260 mg, 0.75 mmol) in tetrahydrofuran (0.3 mL) was added, dropwise, a solution of potassium tert-butoxide (0.75 mL, 1.0 M in tetrahydrofuran). After 15 min, a solution of methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate (95 mg, 0.3 mmol) in tetrahydrofuran (0.3 mL) was added to the above mixture. The resulting mixture was stirred at room temperature for 2.5 h, diluted with ethyl acetate (15 mL) and washed with brine, dried (Na2SO4) and evaporated. The residue was purified by a silica gel chromatography (45 g column), eluting with 15% to 20% of ethyl acetate in hexanes to provide methyl 6-amino-4-(4-fluorophenyl)-2-(1-methylethyl)-5-(2-methoxyethenyl)nicotinate as a E/Z mixture (80 mg, 77%): LCMS (ESI, pos. ion spectrum) m/z 345 (M+H); HPLC (method 3) tR=2.4 min.

Workup

  1. additionwas added
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customThe residue was purified by a silica gel chromatography (45 g column)
  6. washeluting with 15% to 20% of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0fb5ef589eb044808bef91c1f48217a1
Source dataset
uspto-grants-2008_09
Patent number
US07420059B2

Reaction notes

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