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

HRID 533501노트

반응식

HRID 533501 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-331867975e8c426c94d9c62901239378
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853258B2

반응 노트

불러오는 중…