Tetrahydrofuran → 3-Hydroxymethyl-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (1-naphthalen-1-yl-ethyl)-amide

HRID 403176

반응식

HRID 403176 반응식
[OH:1][CH2:2][CH:3]1[CH2:8][O:7][C:6]2[CH:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[C:12]([CH3:13])[C:5]=2[O:4]1.C1COCC1.[C:22]1([C@H:32]([NH2:34])[CH3:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.Cl.CN(C)CCCN=C=NCC>O.CCOCC>[C:22]1([CH:32]([NH:34][C:14]([C:11]2[CH:10]=[CH:9][C:6]3[O:7][CH2:8][CH:3]([CH2:2][OH:1])[O:4][C:5]=3[C:12]=2[CH3:13])=[O:16])[CH3:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724264(+)-1-(1-Naphthyl)ethylamineHCID 687762923-Hydroxymethyl-5-methyl-2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid

생성물 1

HCID 724908523-Hydroxymethyl-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (1-naphthalen-1-yl-ethyl)-amide

시약·촉매·용매 2

HCID 962Water촉매HCID 3283Diethyl Ether용매

실험 절차

To a round bottom flask equipped with magnetic stirring and a nitrogen inlet was added 3-hydroxymethyl-5-methyl-2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid (2.00 g, 8.92 mmol), THF (45 mL), (R)-(+)-1-(1-naphthyl)ethylamine (2.23 mL, 8.92 mmol), and finally 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (1.53 g, 9.81 mmol). This mixture was stirred at room temperature for 36 hours. A few drops of water were added and the mixture stirred for 5 minutes. The reaction was diluted with ether and washed once with 1N HCl, once with saturated sodium bicarbonate(aq), once again with 1N HCl, dried over magnesium sulfate, filtered and evaporated to provide 3-hydroxymethyl-5-methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (1-naphthalen-1-yl-ethyl)-amide. Crystals of acceptable purity for x-ray crystallography were obtained by subliming the material twice under vacuum at 60° C. This x-ray analysis established the regiochemistry and the absolute stereochemistry of the compounds as shown, since the configuration of the naphthylethylamine stereocenter is known and not subject to racemization under the conditions of synthesis. 1H-NMR (300 MHz, CD3COCD3) δ (ppm): 1.71 (d, 3H), 2.22 (s, 3H), 3.80 (m, 2H), 4.06 (m, 1H), 4.23 (m, 2H), 4.32 (m, 1H), 6.09 (m, 1H), 6.65 (d, 1H), 6.87 (d, 1H), 7.55 (m, 3H), 7.69 (m, 2H), 7.83 (d, 1H), 7.94 (d, 1H), 8.35 (d, 1H); TLC Rf=0.12 (1:1 ethyl acetate/hexane).

후처리

  1. customTo a round bottom flask equipped
  2. stirringThis mixture was stirred at room temperature for 36 hours
  3. stirringthe mixture stirred for 5 minutes
  4. washwashed once with 1N HCl, once with saturated sodium bicarbonate(aq), once again with 1N HCl
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

출처 및 근거

ORD 기록
ord-dfe70dfc9507449eb36262542e01aabb
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748125B2

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