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Isobutyryl chloride → [(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate

HRID 58960
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HRID 58960 반응식
[C:1]([O:5][C:6]([N:8]([C@H:16]1[CH2:24][O:23][CH2:22][C@H:21]([CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)[C@@H:20]([OH:36])[C@H:19]([CH3:37])[O:18][C:17]1=[O:38])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:39](Cl)(=[O:43])[CH:40]([CH3:42])[CH3:41]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:11]([O:10][C:9]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@@H:16]1[C:17](=[O:38])[O:18][C@@H:19]([CH3:37])[C@H:20]([O:36][C:39](=[O:43])[CH:40]([CH3:42])[CH3:41])[C@@H:21]([CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)[CH2:22][O:23][CH2:24]1)=[O:15])([CH3:13])([CH3:14])[CH3:12]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 2

HCID 62325Isobutyryl chlorideHCID 117974424tert-butyl N-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate

생성물 1

HCID 117974254[(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate수율 82.2%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine
촉매
HCID 6344Dichloromethane용매2회

실험 절차

To a solution of tert-butyl N-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate (290 mg, 0.548 mmol) and DMAP (201 mg, 1.64 mmol) in CH2Cl2 (2.7 mL) was added isobutyryl chloride (86 μL, 0.821 mmol) slowly to the flask and the resulting solution was stirred at room temperature for 20 h. The reaction mixture was dissolved in CH2Cl2 (4 mL), treated with Celite®, the solvent evaporated, and the adsorbed crude material purified by flash chromatography (SiO2, 0→15% EtOAc/hexanes) to provide [(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate (270 mg, 82%) as a white powder: mp 130-132° C.; 1H NMR (400 MHz, CDCl3) δ 8.01-7.93 (m, 1H), 7.84 (dd, J=8.0, 1.5 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.54-7.41 (m, 2H), 7.37 (dd, J=8.2, 7.0 Hz, 1H), 7.28 (dd, J=7.0, 1.3 Hz, 1H), 5.20 (dd, J=8.7, 5.7 Hz, 1H), 5.11 (app t, J=9.3 Hz, 1H), 5.08-4.97 (m, 1H), 4.06 (dd, J=11.8, 5.7 Hz, 1H), 3.86 (dd, J=11.9, 8.7 Hz, 1H), 3.66 (d, J=11.0 Hz, 1H), 3.50 (dd, J=10.8, 6.4 Hz, 1H), 3.23 (dd, J=14.0, 3.1 Hz, 1H), 2.74-2.55 (m, 2H), 2.37-2.20 (m, 1H), 1.42 (s, 18H), 1.37 (d, J=6.2 Hz, 3H), 1.26 (app dd, J=7.0, 4.4 Hz, 6H); ESIMS m/z 622 ([M+Na]+).

후처리

  1. additiontreated with Celite®
  2. customthe solvent evaporated
  3. customthe adsorbed crude material purified by flash chromatography (SiO2, 0→15% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-8244359ac43b40219e34a9e8d21e5cdd
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09439422B2

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