Hydrochloric Acid → 1'-{[4-(Trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'h)-one

HRID 2385550노트

반응식

HRID 2385550 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22].[F:23][C:24]([F:34])([F:33])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([CH2:31]O)[CH:26]=1.C(P(CCCC)CCCC)CCC.N(C(OCC)=O)=NC(OCC)=O.Cl>O1CCCC1.CS(C)=O>[F:34][C:24]([F:23])([F:33])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([CH2:31][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:21]4[C:12](=[CH:13][C:14]5[O:19][CH2:18][CH2:17][O:16][C:15]=5[CH:20]=4)[O:11][CH2:10]3)[C:2]2=[O:22])[CH:26]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 13831TributylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 147614592-(Hydroxymethyl)-4-(trifluoromethyl)pyridineHCID 58224164Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro

생성물 1

HCID 593521621'-{[4-(Trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'h)-one수율 14.2%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.753 g, 2.55 mmol), [4-(trifluoromethyl)pyridin-2-yl]methanol (Ashimori et al., Chem. Pharm. Bull. (1990) 38:2446-2458) (0.655 g, 3.70 mmol) and tri-n-butylphosphine (0.93 mL, 3.7 mmol) in anhydrous tetrahydrofuran (20 mL) and anhydrous dimethylsulfoxide (0.2 mL) at ambient temperature was added over a period of 10 min a solution of diethyl azodicarboxylate (0.64 mL, 4.1 mmol) in anhydrous tetrahydrofuran (10 mL). The reaction mixture was stirred at ambient temperature for 3 h and was poured into 1 M hydrochloric acid (50 mL). The mixture was extracted with diethyl ether (3×50 mL) and the combined organic extracts were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography and eluted with a 80% to 100% gradient of dichloromethane in hexanes, followed by a 0% to 20% gradient of ethyl acetate in dichloromethane and recrystallization from methanol afforded 1′-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.164 g, 10%) as a colorless solid: mp 154-155° C. (methanol); 1H NMR (300 MHz, CDCl3) δ8.76 (d, J=5.1 Hz, 1H), 7.51 (s, 1H), 7.44 (d, J=5.1 Hz, 1H), 7.24-7.16 (m, 2H), 7.08-7.01 (m, 1H), 6.86 (d, J=7.7 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H), 5.27 (d, J=16.1 Hz, 1H), 5.04 (d, J=16.1 Hz, 1H), 4.95 (d, J=9.0 Hz, 1H), 4.69 (d, J=9.0 Hz, 1H), 4.23-4.11 (m, 4H); 13C NMR (75 MHz, CDCl3) δ177.8, 157.3, 155.3, 150.8, 144.8, 141.9, 139.8, 138.5, 132.3, 129.0, 124.1, 123.9, 121.1, 118.7, 117.6, 111.8, 109.3, 99.5, 80.1, 64.7, 64.0, 58.2, 45.8; MS (ES+) m/z 455.0 (M+1).

후처리

  1. extractionThe mixture was extracted with diethyl ether (3×50 mL)
  2. washthe combined organic extracts were washed with brine (50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography
  7. washeluted with a 80% to 100% gradient of dichloromethane in hexanes
  8. customfollowed by a 0% to 20% gradient of ethyl acetate in dichloromethane and recrystallization from methanol

출처 및 근거

ORD 기록
ord-25ab7f299e3e4f8c83b03ea1ddf2d2e5
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08263606B2

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