Furan-3-boronic acid → HCID 57063305, compound

HRID 1602981Notes

Reaction equation

HRID 1602981 reaction equation
Br[C:2]1[CH:33]=[CH:32][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C@@H:17]([C:29]([OH:31])=[O:30])[C:18]([S:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)([CH3:20])[CH3:19])(=[O:15])=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[O:34]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35]1>C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].CCO.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>[O:34]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:8]=[CH:9][C:10]([S:13]([NH:16][C@@H:17]([C:29]([OH:31])=[O:30])[C:18]([S:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)([CH3:20])[CH3:19])(=[O:14])=[O:15])=[CH:11][CH:12]=3)=[CH:32][CH:33]=2)=[CH:35]1

Participants

7

Reactant 2

HCID 2734358Furan-3-boronic acidHCID 57102378HCID 57102378, compound

Product 1

HCID 57063305HCID 57063305, compoundYield 77.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 221 mg (0.40 mmol) of N-[4-(4-bromophenoxy) benzenesulfonyl]--S--[(pyrid-2-yl)methyl]-D-penicillamine (from example 3(d)) in 2 mL of benzene and 2 mL of 2M aqueous Na2CO3 solution was added a solution of 71 mg (0.48 mmol) of 3-furan boronic acid (J. Org. Chem. 1984, 49, 5237-5243) in 2 mL of EtOH. To the resulting mixture was added solid Pd(PPh3)4 (46 mg, 0.04 mmol) under a flow of Ar. The mixture was heated at 80° C. with vigorous stirring for 72 hours, cooled to room temperature, and partitioned between ehtyl acetate and AcOH/H2O buffer (pH 3). The aqueous layer was adjusted to pH of 3 by adding AcOH, then extracted with EtOAc (2×70 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residual yellow solid was chromatographed on silica gel, eluting first with CH2Cl2, then with 10% methanol in dichloromethane to elute the product fractions. After concentration of the product-containing fractions, the residue was triturated with hexane/t-butyl methyl ether, and the solid was collected by filtration. The solid was dried in high vacuum to give 166.1 mg (77%) of N-[4-(4-(furan-3-yl)phenoxy)benzenesulfonyl]--S--[(pyrid-2-yl)methyl]-D-penicillamine as a yellow solid: mp 185-189° C.; 1H--NMR (CDCl3) δ 1.40 (s, 3H) 1.44 (s, 3H), 3.32-4.01 (m, 3H), 6.83 (s, 1H), 7.10-7.13 (m, 4H), 7.22-7.23 (m, 2H), 7.57-7.92 (m, 8H), 8.42 (d, J=4 Hz, 2H).

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between ehtyl acetate and AcOH/H2O buffer (pH 3)
  3. additionby adding AcOH
  4. extractionextracted with EtOAc (2×70 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residual yellow solid was chromatographed on silica gel
  9. washeluting first with CH2Cl2
  10. washwith 10% methanol in dichloromethane to elute the product fractions
  11. customAfter concentration of the product-containing fractions, the residue was triturated with hexane/t-butyl methyl ether
  12. filtrationthe solid was collected by filtration
  13. customThe solid was dried in high vacuum

Sources & evidence

ORD record
ord-b02f06a677304bf7a307436471faaef1
Source dataset
uspto-grants-1999_11
Patent number
US05985900

Reaction notes

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