Pyridine → HCID 86695505, compound

HRID 525616Notes

Reaction equation

HRID 525616 reaction equation
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

Participants

9

Reactant 7

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 449047Hydrogen peroxide waterHCID 516919Sodium BisulfateHCID 86695504HCID 86695504, compound

Product 1

HCID 86695505HCID 86695505, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Trifluoroacetic acid (51.6μL) is added to the product of step 3, Example 95A (0.168 g, 0.335 mmol) and pyridine (54.2μL, 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, 60μL, 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.

Workup

  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

Sources & evidence

ORD record
ord-4e129029649944cda79d981eb838d78c
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

Loading…