Boronic Acid → HCID 58909462, compound

HRID 1985045Notes

Reaction equation

HRID 1985045 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:25])[CH3:24])[C@H:7]([OH:21])[CH2:8][NH:9][C@@H:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=2)[O:13][CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].B(O)O.CCCC[N+:45]([CH2:54][CH2:55][CH2:56][CH3:57])(CCCC)CCCC.[F-]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:25])[CH3:24])[C@H:7]([OH:21])[CH2:8][NH:9][C@@H:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:56]3[CH:55]=[CH:54][NH:45][CH:57]=3)[CH:18]=2)[O:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 61668Boronic AcidHCID 62657Potassium Phosphate, TribasicHCID 2724141Tetrabutylammonium FluorideHCID 10255974HCID 10255974, compound

Product 1

HCID 58909462HCID 58909462, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

To a solution of N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-{[(4S)-6-iodo-3,4-dihydro-2H-chromen-4-yl]amino}propyl)acetamide (0.300 g, 0.58 mmol) and anhydrous THF (5 mL) was added Pd(dppf)Cl2 (0.030 g, 0.03 mmol) and K3PO4 (2.9 mL, 5.80 mmol). To this mixture was added boronic acid (0.310 g, 1.16 mmol) (J. Org. Chem. 1992, 57, 1653) and the reaction mixture was heated to 65° C. overnight under nitrogen with stirring. Reaction was quenched with deionized water and then extracted with ethyl acetate. Organic layers were washed with brine, then dried with MgSO4, filtered, and concentrated in vacuo. The TIPS-protected compound (0.100 g, 0.16 mmol) was dissolved in THF (3 mL) and then 0.1M solution of TBAF in THF (0.32 mL, 0.32 mmol) was added. Reaction mixture was stirred for 2 h, then concentrated in vacuo. Dissolved in ethyl acetate, filtered through silica gel plug, then concentrated in vacuo to give the desired product as an amber oil (130 mg), which is purified by reverse phase prep-HPLC. HRMS (ESI); calcd for C25H27N3O3F2+H1 456.2099, found 456.2092.

Workup

  1. customReaction
  2. customwas quenched with deionized water
  3. extractionextracted with ethyl acetate
  4. washOrganic layers were washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customReaction mixture
  9. stirringwas stirred for 2 h
  10. concentrationconcentrated in vacuo
  11. dissolutionDissolved in ethyl acetate
  12. filtrationfiltered through silica gel plug
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a140f21eaf72404abe6f7953ffc425c9
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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