Triethylamine → (+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533501ノート

反応式

HRID 533501 の反応式
C(N(CC)CC)C.N1(O)C2C=CC=CC=2N=N1.[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]([CH3:35])([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([OH:30])=O)=[CH:21][CH:20]=1.[O:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH:37]1[O:42][NH2:43].Cl.C(N=C=NCCCN(C)C)C>ClCCl>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:25][CH2:26][C:27]([CH3:35])([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([NH:43][O:42][CH:37]2[CH2:38][CH2:39][CH2:40][CH2:41][O:36]2)=[O:30])=[CH:23][CH:24]=1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 66577906(+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)butanoic acid

生成物 1

HCID 76445393(+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide収率 76.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Triethylamine (5.49 g, 54.3 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol (7.5 g, 49 mmol) were added to a solution of the (+/−)-4-(4-bromophenyl)-2-methyl-2-(methylsulfonyl)butanoic acid (9.1 g, 27.1 mmol) in dichloromethane (100 mL). After 10 minutes O-tetrahydro-2H-pyran-2yl-hydroxylamine (4.6 g, 39 mmol) was added followed by N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (EDCI) (7.2 g, 38 mmol). After 12 h the reaction was quenched by the addition of saturated aqueous NaHCO3. The layers were separated and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate 7:3-6:4) afforded the title compound as a white solid (9.0 g, 76%). LCMS m/z 434.1 (M+1) 1H NMR (400 MHz, DMSO-d6) δ ppm 1.54 (d, J=3.90 Hz, 6H) 1.69 (br. s., 3H) 1.78-2.06 (m, 1H) 2.27-2.55 (m, 2H) 2.59-2.72 (m, 1H) 3.03 (d, J=6.64 Hz, 3H) 3.50 (d, J=11.32 Hz, 1H) 3.95-4.22 (m, 1H) 4.97 (d, J=9.37 Hz, 1H) 7.22 (dd, J=8.39, 4.49 Hz, 2H) 7.49 (d, J=8.20 Hz, 2H) 11.36 (br. s., 1H)

後処理

  1. customAfter 12 h the reaction was quenched by the addition of saturated aqueous NaHCO3
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography on silica gel (hexanes/ethyl acetate 7:3-6:4)

出典と根拠

ORDレコード
ord-331867975e8c426c94d9c62901239378
出典データセット
uspto-grants-2014_10
特許番号
US08853258B2

反応ノート

読み込み中…