Triphenylphosphine → 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

HRID 2089498노트

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HRID 2089498 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH2:8][C:7]([CH3:15])([CH3:14])[CH:6]2O.[NH:17]1[CH:21]=[C:20]([C:22]([O:24][CH:25]([CH3:27])[CH3:26])=[O:23])[N:19]=[CH:18]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC)=O)=NC(OC)=O>C1COCC1>[CH:25]([O:24][C:22]([C:20]1[N:19]([CH:6]2[C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9](=[O:13])[CH2:8][C:7]2([CH3:15])[CH3:14])[CH:18]=[N:17][CH:21]=1)=[O:23])([CH3:27])[CH3:26]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 351621Azodicarboxylic acid dimethyl esterHCID 675467026-methoxy-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-naphthalen-1-oneHCID 178459416HCID 178459416, 화합물

생성물 1

HCID 591993943-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of 6-methoxy-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-naphthalen-1-one (0.75 g, 3.28 mmol), isopropyl 4-imidazolecarboxylate (0.36 g, 2.30 mmol), which can be prepared as described in Example 1, in THF (20 mL) at 0° C. is added triphenylphosphine (0.87 g, 3.28 mmol), followed by dimethyl azodicarboxylate (40% in toluene, 1.2 mL, 3.28 mmol) and the cooling bath is removed. After 16 hours, the mixture is diluted with ethyl acetate and washed twice with half-saturated brine. The mixture is extracted five times with 1M aqueous HCl (20 mL portions). The acidic aqueous phases are then cooled to 0° C., the pH is adjusted to ca. 9 with 2M aqueous NaOH at 0° C. and the aqueous phase is extracted three times with dichloromethane. The combined organic phases are dried over MgSO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 49:1) to give 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 357.1 (M+H)+ The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester 1H NMR (400 MHz, MeOD) δ ppm 1.00 (s, 3 H), 1.23 (s, 3 H), 1.48 (d, J=6.3 Hz, 3 H), 1.50 (d, J=6.3 Hz, 3 H), 2.61 (d, J=17.4 Hz, 1 H), 2.78 (d, J=17.4 Hz, 1 H), 3.89 (s, 3H), 5.34-5.47 (m, 1 H), 6.85 (d, J=2.3 Hz, 1 H), 6.95 (s, 1 H), 7.20 (dd, J=8.6, 2.3 Hz, 1 H), 8.16 (d, J=8.6 Hz, 1 H), 8.40 (s, 1 H), 8.94 (s, 1 H).

후처리

  1. customthe cooling bath is removed
  2. additionthe mixture is diluted with ethyl acetate
  3. washwashed twice with half-saturated brine
  4. extractionThe mixture is extracted five times with 1M aqueous HCl (20 mL portions)
  5. customis adjusted to ca. 9 with 2M aqueous NaOH at 0° C.
  6. extractionthe aqueous phase is extracted three times with dichloromethane
  7. dry with materialThe combined organic phases are dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 49:1)

출처 및 근거

ORD 기록
ord-d6030bb0170b4830b77a7aef3802b166
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08436035B2

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