Ethyl Acetate → N-(5'-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 1467925노트

반응식

HRID 1467925 반응식
[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]3)[C:12]2=O)=[CH:8][CH:7]=1.[CH3:22][C:23]([S:26]([NH2:28])=[O:27])([CH3:25])[CH3:24].CCOC(C)=O>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC.O>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9](=[CH:8][CH:7]=1)[CH2:10][C:11]1([CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]1)[C:12]2=[N:28][S:26]([C:23]([CH3:25])([CH3:24])[CH3:22])=[O:27]

참가 물질

6

반응물 3

HCID 8857Ethyl AcetateHCID 3382465Tert-Butanesulfinamide2회HCID 679796486'-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one2회

생성물 1

HCID 86706683N-(5'-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide수율 23%

시약·촉매·용매 2

HCID 76524Titanium tetraethoxide촉매2회HCID 962Water용매

실험 절차

6′-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 21, 0.91 g, 3.11 mmol), 2-methylpropane-2-sulfinamide (0.566 g, 4.67 mmol) and titanium(IV) ethoxide (1.283 mL, 6.23 mmol) were dissolved in 2-Me THF (8 mL) and heated to reflux over a weekend. More 2-methyl-2-propanesulfinamide (0.189 g, 1.56 mmol) and titanium(IV) ethoxide (0.325 mL, 1.56 mmol) were added, and the mixture was refluxed overnight. The reaction was cooled to r.t. EtOAc (50 mL) and water (10 mL) were added under stirring. The mixture were let to stand still for 1 h. The organic phase was collected by filtration, dried, and concentrated. The residue was purified by flash column chromatography using a gradient of 0-40% EtOAc in heptane, to give 0.278 g (23% yield) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.33 (s, 9 H) 1.45-1.54 (m, 4 H) 1.87 (br. s., 1 H) 2.03 (dd, 2 H) 2.14-2.19 (m, 1 H) 2.20-2.25 (m, 1 H) 2.93-3.01 (m, 2 H) 3.71-3.80 (m, 1 H) 4.13-4.18 (m, 2 H) 4.59-4.66 (m, 1 H) 4.69-4.75 (m, 1 H) 7.11 (dd, 1 H) 7.29 (s, 1 H); MS (ES+) m/z 396.11 [M+H]+.

후처리

  1. temperatureheated
  2. temperatureto reflux over a weekend
  3. temperaturethe mixture was refluxed overnight
  4. filtrationThe organic phase was collected by filtration
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-e9947a1615cc402fa0c5fcf4c061ac75
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000182B2

반응 노트

불러오는 중…