Lithium Chloride → tert-butyl 4-[4-fluoro-3-(methoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 643554ノート

反応式

HRID 643554 の反応式
[F:1][C:2]1[CH:11]=[CH:10][C:9](I)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Li+].[Cl-].C[Sn](C)(C)[C:17]1[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:21][CH:22]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C([O-])(O)=O.[Na+]>CN(C=O)C.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[CH:11]=[CH:10][C:9]([C:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

参加物

9

反応物 5

HCID 433294Lithium ChlorideHCID 516892Sodium BicarbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 220229891-t-Butoxycarbonyl-4-trimethylstannyl-1,2,5,6-tetrahydropyridineHCID 24820379Methyl 2-fluoro-5-iodobenzoate

生成物 1

HCID 57880514tert-butyl 4-[4-fluoro-3-(methoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
90 °C

実験手順

Methyl 2-fluoro-5-iodobenzoate (5.01 g, 17.9 mmol) was combined with LiCl (1.52 g, 35.7 mmol) and tert-butyl 4-(trimethylstannyl)-3,6-dihydropyridine-1(2H)-carboxylate (4.28 g, 12.3 mmol) in 100 mL of DMF. After stirring for 20 min under a nitrogen atmosphere, Pd2dba3 (218 mg, 0.238 mmol) and P(2-furyl)3 (276 mg, 1.19 mmol) were added and the reaction mixture was warmed to 90° C. under a nitrogen atmosphere and stirred for 1 h 45 min. The reaction mixture was then stirred at rt overnight. Then the reaction temperature was brought again to 90° C. for 1 h. To the mixture was added saturated NaHCO3 solution and brine. The resulting aqueous mixture was then extracted three times with ether. The ethereal layers were combined and washed four times with water, dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 5-25% gradient of ethyl actetate/hexanes, over 2L volume) gave tert-butyl 4-[4-fluoro-3-(methoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate. 1H NMR (500 MHz, CDCl3) δ 7.94 (dd, J=7.0, 2.5 Hz, 1H), 7.53 (m, 1H), 7.13 (dd, J=10, 8.5 Hz, 1H), 6.07 (br s, 1H), 4.10 (br s, 2H), 3.96 (s, 3H), 3.66 (t, 6 Hz, 2H), 2.53 (br m, 2H), 1.52 (s, 9H). ESI-MS calc. for C18H22FNO4: 335; Found: 236 (M+Boc+H).

後処理

  1. stirringstirred for 1 h 45 min
  2. stirringThe reaction mixture was then stirred at rt overnight
  3. waitThen the reaction temperature was brought again to 90° C. for 1 h
  4. extractionThe resulting aqueous mixture was then extracted three times with ether
  5. washwashed four times with water
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by MPLC (silica, 5-25% gradient of ethyl actetate/hexanes, over 2L volume)

出典と根拠

ORDレコード
ord-ad2e6d550f8f4e80b2da191386143494
出典データセット
uspto-grants-2010_04
特許番号
US07700591B2

反応ノート

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