Ethanol → 4-(4-(furan-3-yl)phenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid

HRID 23173

Reaction equation

HRID 23173 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH:16]3[CH:21]([C:22]([OH:24])=[O:23])[NH:20][CH2:19][CH2:18][S:17]3)(=[O:15])=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[O:27]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28]1.C(O)C>C1C=CC=CC=1.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>[O:27]1[CH:31]=[CH:30][C:29]([C:2]2[CH:26]=[CH:25][C:5]([O:6][C:7]3[CH:8]=[CH:9][C:10]([S:13]([CH:16]4[CH:21]([C:22]([OH:24])=[O:23])[NH:20][CH2:19][CH2:18][S:17]4)(=[O:15])=[O:14])=[CH:11][CH:12]=3)=[CH:4][CH:3]=2)=[CH:28]1

Participants

7

Reactant 3

HCID 702EthanolHCID 2734358Furan-3-boronic acidHCID 865886714-(4-bromophenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid

Product 1

HCID 865886704-(4-(furan-3-yl)phenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acidYield 67%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.45 g (1.0 mmol) of 3(S)-4-(4-(4-bromophenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid and 0.11 g (1.0 mmol) of 3-furan boronic acid (J. Org. Chem. 1984, 49, 5237-5243) in 2 mL of benzene, 2 mL of 2M aq. sodium carbonate, and 1.5 mL of ethanol was deoxygenated with a stream of argon for 15 minutes, and then 115 mg (0.1 mmol) of tetrakis(triphenylphosphine)palladium was added and the mixture was heated at 80° C. for six days. After cooling to room temperature, the mixture was partitioned between ethyl acetate and pH 4 citrate buffer. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by chromatography on silica gel, eluting with a gradient from dichloromethane to 5% methanol in dichloromethane, to provide 3(S)-4-(4-(4-(furan-3-yl)phenoxy)benzenesulfonyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid (0.317 g, 67%) as a sticky solid foam. FAB+MS Calcd for M+Cs+=606.0021. Obs 606.0036; 1H NMR (CDCl3) δ 7.72-7.43 (m, 6H), 7.04 (d, 2H, J=8.46 Hz), 7.00 (d, 2H, J=8.82 Hz), 6.67 (s, 1H), 4.51 (s, 1H), 4.1-3.9 (bm, 1H), 3.7-3.6 (bm, 1H), 3.2-3.1 (bm, 1H), 2.42 (bd, 1H, J=12.87 Hz), 1.61 (s, 3H), 1.38 (s, 3H)

Workup

  1. customwas deoxygenated with a stream of argon for 15 minutes
  2. temperatureAfter cooling to room temperature
  3. customthe mixture was partitioned between ethyl acetate and pH 4 citrate buffer
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel
  9. washeluting with a gradient from dichloromethane to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-4680cbedb8364560ab87f775821d48ad
Source dataset
uspto-grants-2005_02
Patent number
US06849732B2

Linked notes

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