Pyridine → benzyl (1-(5-(4-((1R,2S)-1-((bis(benzyloxy)-phosphoryl)oxy)-2-(2,2-difluoroacetamido)-3-fluoropropyl)phenyl)pyridin-2-yl)ethyl)carbamate

HRID 1520549노트

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HRID 1520549 반응식
FC(F)(F)C(O)=[O:4].[F:8][CH:9]([F:43])[C:10]([NH:12][C@H:13]([CH2:41][F:42])[C@@H:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH3:29])=[N:26][CH:27]=2)=[CH:18][CH:17]=1)[OH:15])=[O:11].N1C=CC=CC=1.C1COCC1.[CH2:55]([O:62][P:63]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)N(C(C)C)C(C)C)[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1.OO.O.S(=O)(=O)(O)[O-].[Na+]>O>[CH2:72]([O:71][P:63]([O:15][C@H:14]([C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH3:29])=[N:26][CH:27]=2)=[CH:20][CH:21]=1)[C@H:13]([NH:12][C:10](=[O:11])[CH:9]([F:8])[F:43])[CH2:41][F:42])([O:62][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:4])[C:73]1[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=1

참가 물질

9

반응물 7

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 449047Hydrogen peroxide waterHCID 516919Sodium BisulfateHCID 86695504benzyl (1-(5-(4-((1R,2S)-2-(2,2-difluoroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)pyridin-2-yl)ethyl)carbamate

생성물 1

HCID 86695505benzyl (1-(5-(4-((1R,2S)-1-((bis(benzyloxy)-phosphoryl)oxy)-2-(2,2-difluoroacetamido)-3-fluoropropyl)phenyl)pyridin-2-yl)ethyl)carbamate

시약·촉매·용매 1

HCID 962Water용매

실험 절차

Trifluoroacetic acid (51.6 μL) is added to the product of step 3, Example 95A (0.168 g, 0.335 mmol) and pyridine (54.2 μL, 0.67 mmol) in THF (4.4 mL, 54 mmol) at 0° C. After 5 minutes, bis(benzyloxy)(diisopropylamino)phosphine (0.219 mL, 0.586 mmol) is added. After allowing to warm to room temperature the mixture is stirred for 1 hour. 30% hydrogen peroxide/water (30:70, 60 μL, 0.586 mmol) is added. After 1 hour sodium bisulfate (4 mL) is added and water (10 mL) is added. The reaction mixture is extracted with ethylacetate (2×15 mL). The combined organics are dried over MgSO4, filtered and evaporated to give the crude product, which is purified by silica chromatography eluting from 25% ethylacetate/heptanes to neat ethylacetate to give the title product (241 mg): m/z: 761.25.

후처리

  1. extractionThe reaction mixture is extracted with ethylacetate (2×15 mL)
  2. dry with materialThe combined organics are dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto give the crude product, which
  6. customis purified by silica chromatography
  7. washeluting from 25% ethylacetate/heptanes to neat ethylacetate

출처 및 근거

ORD 기록
ord-f81b824cc69646658d885e31e4021d94
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073894B2

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