Sodium Carbonate → (4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1500299노트

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HRID 1500299 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2(F)[CH2:11][S:10](=[O:13])(=[O:12])[CH2:9]2)=[N:6][CH:7]=1.[C:15]([O:19][C:20]([N:22]1[C@H:26]([CH2:27][F:28])[C@@H:25]([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[O:24][C:23]1([CH3:45])[CH3:44])=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(O)C.O>[O:12]=[S:10]1(=[O:13])[CH:11]=[C:8]([C:5]2[N:6]=[CH:7][C:2]([C:32]3[CH:31]=[CH:30][C:29]([C@H:25]4[O:24][C:23]([CH3:44])([CH3:45])[N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[C@@H:26]4[CH2:27][F:28])=[CH:34][CH:33]=3)=[CH:3][CH:4]=2)[CH2:9]1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylateHCID 867131853-(5-Bromopyridin-2-yl)-3-fluorothietane 1,1-dioxide

생성물 1

HCID 86713187(4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 86587398Ethanol toluene water용매

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온도
80 °C

실험 절차

The solution of the product of step 3, Example 18 (0.15 g, 0.538 mmol, 1 eq), (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (previously described in US2004082553, Example 20, intermediate 19, 0.234 g, 0.538 mmol, 1 eq) and sodium carbonate (0.171 g, 1.613 mmol, 3 eq) in mixture of Toluene/Ethanol/Water (1:1:0.5, 2.5 mL) is degassed with nitrogen for 30 minutes in sealed tube. To the resulting reaction mixture tetrakis(triphenylphosphine)palladium(0) (0.062 g, 0.054 mmol, 0.1 eq) is added. Resulting reaction mixture is heated at 80° C. for 6 hours. The reaction mixture is quenched with water (15 mL) and extracted with ethyl acetate (3×25 mL). Combined organic layer is dried over sodium sulphate and concentrated in vacuo. The crude compound is purified by column chromatography using (100-200 mesh silica). Desired compound is eluted with 30% ethyl acetate in hexane to afford title compound as yellow solid (0.16 g): 1H-NMR (400 MHz, DMSO) δ: 1.43 (bs, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 3.85-3.90 (m, 1H), 4.47-4.59 (m, 1H), 4.75-4.84 (m, 1H), 5.05 (s, 2H), 5.15 (d, 1H, J=7.16 Hz), 7.62 (d, 2H, J=8.12 Hz), 7.76 (s, 1H), 7.87 (d, 2H, J=8.2 Hz), 7.93 (d, 1H, J=8.12 Hz), 8.31-8.34 (dd, 1H, J1=8.24 Hz, J2=2.16 Hz). 9.07 (d, 1H, J=1.88 Hz). LC-MS (m/z): [M+H] 489.1.

후처리

  1. customis degassed with nitrogen for 30 minutes in sealed tube
  2. additionis added
  3. customResulting
  4. customreaction mixture
  5. customThe reaction mixture is quenched with water (15 mL)
  6. extractionextracted with ethyl acetate (3×25 mL)
  7. dry with materialCombined organic layer is dried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe crude compound is purified by column chromatography
  10. washDesired compound is eluted with 30% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-092e41b5151449aca5db6bb7b359ffc3
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206126B2

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