Sodium Carbonate → methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate

HRID 1959474ノート

反応式

HRID 1959474 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)O1.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.[C:41]([O:45][C:46]([N:48]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:49]1[C:50]([C:56]([O:58][CH3:59])=[O:57])=[N:51][C:52](Br)=[CH:53][N:54]=1)=[O:47])([CH3:44])([CH3:43])[CH3:42].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.Cl[Pd]Cl.O>[C:63]([O:62][C:60]([N:48]([C:46]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:47])[C:49]1[C:50]([C:56]([O:58][CH3:59])=[O:57])=[N:51][C:52]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)=[CH:53][N:54]=1)=[O:61])([CH3:66])([CH3:65])[CH3:64]

参加物

9

反応物 4

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 86660188Methyl 3-(bis(tert-butoxycarbonyl)amino)-6-bromopyrazine-2-carboxylate

生成物 1

HCID 66745644methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate収率 97.6%

試薬・触媒・溶媒 4

HCID 24290Palladium Chloride触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A suspension of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (858 mg, 2.8 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (164 mg, 0.23 mmol), methyl 3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazine-2-carboxylate (1.0 g, 2.3 mmol), and Na2CO3 (490 mg, 4.6 mmol) under an atmosphere of nitrogen in toluene (15 mL) and water (2 mL) was heated to 95° C. for 2 h. The reaction mixture was diluted with ethyl acetate, washed with 1N HCl, 50% saturated sodium bicarbonate solution, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified via silica gel column chromatography using 10-50% ethyl acetate/hexane to provide methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate (1.2 g, 97%) as a amber oil. 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 6.97 (s, 1H), 4.12 (s, 2H), 3.89 (s, 3H), 3.57 (t, J=5.2 Hz, 2H), 2.61 (s, 2H), 1.43 (s, 9H), 1.34 (s, 18H). LC/MS m/z 535.5 [M+H]+.

後処理

  1. washwashed with 1N HCl, 50% saturated sodium bicarbonate solution, and brine
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified via silica gel column chromatography

出典と根拠

ORDレコード
ord-f2210440f10c49128aad07dd52024595
出典データセット
uspto-grants-2013_04
特許番号
US08410112B2

反応ノート

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