Pyridine → (3S,4aR,6aR,11aR,11bR)-7,9-dimethoxy-4,4,6a,11b-tetramethyl-2,3,4,4a,5,6,6a,11,11a,11b-decahydro-1H-benzo[a]fluoren-3-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoate

HRID 1466730

반응식

HRID 1466730 반응식
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[C:12]2[C:4]=1[C@@:5]1([CH3:26])[C@H:10]([CH2:11]2)[C@@:9]2([CH3:25])[CH2:18][CH2:19][C@H:20]([OH:24])[C:21]([CH3:23])([CH3:22])[C@@H:8]2[CH2:7][CH2:6]1.N1C=CC=CC=1.CN(C1C=CC=CN=1)C.[CH3:42][O:43][C@:44]([C:54]([F:57])([F:56])[F:55])([C:51](Cl)=[O:52])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C(Cl)Cl>[F:55][C:54]([F:56])([F:57])[C@:44]([O:43][CH3:42])([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:51]([O:24][C@H:20]1[CH2:19][CH2:18][C@:9]2([CH3:25])[C@@H:10]3[C@@:5]([CH3:26])([CH2:6][CH2:7][C@H:8]2[C:21]1([CH3:22])[CH3:23])[C:4]1[C:12](=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=1[O:2][CH3:1])[CH2:11]3)=[O:52]

참가 물질

6

반응물 4

HCID 1049PyridineHCID 218852-DimethylaminopyridineHCID 3080792(-)-alpha-Methoxy-alpha-(trifluoromethyl)phenylacetyl chlorideHCID 56837778(3S,4aR,6aR,11aR,11bR)-7,9-Dimethoxy-4,4,6a,11b-tetramethyl-2,3,4,4a,5,6,6a,11,11a,11b-decahydro-1H-benzo[a]fluoren-3-ol

생성물 1

HCID 68016598(3S,4aR,6aR,11aR,11bR)-7,9-dimethoxy-4,4,6a,11b-tetramethyl-2,3,4,4a,5,6,6a,11,11a,11b-decahydro-1H-benzo[a]fluoren-3-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Alcohol 5b (219 mg, 0.610 mmol) was dissolved in 4 mL of methylene chloride (DCM). To this mixture was added pyridine (0.074 mL, 0.92 mmol) and dimethylaminopyridine (DMAP) (7.4 mg, 0.061 mmol), and the mixture was taken to 0° C. To this mixture was added (R)-(−)-MTPA-Cl (170 mg, 0.671 mmol), and the mixture was allowed to warm to room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl (50 mL), and the aqueous layer was extracted 3 times with methylene chloride (3×50 mL). The organic extracts were combined and dried with MgSO4 and concentrated. A 1H NMR (400 MHz) spectrum of the crude mixture showed the absence of diastereomers, meaning that alcohol 5b was enantiomerically pure after crystallization. The product mixture was then purified using flash chromatography (hexanes:ethyl acetate 12:1) to give 10b quantitatively. 1H NMR (400 MHz, CDCl3) δ 7.54 (m, 2H), 7.41 (m, 3H), 6.40 (d, J=1.8 Hz, 1H), 6.26 (d, J=1.9 Hz, 1H), 4.72 (dd, J=12, 4.9 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 3H), 3.54 (s, 3H), 2.62 (m, 1H), 2.51 (dd, J=14, 6.2 Hz, 1H), 2.46 (dd, J=8.4, 2.9 Hz, 1H), 1.85-1.76 (m, 1H), 1.74-1.67 (m, 3H), 1.65-1.57 (m, 3H), 1.23 (td, J=13, 4.2 Hz, 1H), 1.07 (s, 3H), 1.04 (s, 3H), 1.04 (m, 1H), 0.92 (s, 3H), 0.87 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.3, 159.5, 155.8, 144.7, 133.2, 132.3, 129.5, 128.3 (2C), 127.6 (2C), 124.9, 122.0, 101.9, 96.9, 84.5, 64.2, 56.2, 55.4, 55.3, 55.1, 46.1, 38.1, 38.0, 37.9, 36.5, 29.5, 28.1, 23.0, 20.3, 19.0, 16.2, 16.1. ESIMS [M+Na]+ calcd for C33H41O5F3Na 597.2804, found 597.2814. [α]24D=−31.76°.

후처리

  1. customwas taken to 0° C
  2. customThe reaction was quenched with saturated aqueous NH4Cl (50 mL)
  3. extractionthe aqueous layer was extracted 3 times with methylene chloride (3×50 mL)
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated
  6. customafter crystallization
  7. customThe product mixture was then purified

출처 및 근거

ORD 기록
ord-2105b25229b2474e95da28446c41a2d8
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000050B2

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