4-Toluenesulfonyl chloride → HCID 22118341, compound

HRID 1274871Notes

Reaction equation

HRID 1274871 reaction equation
[CH2:1]([Li])[CH3:2].[CH3:4][C:5]1[O:10][CH2:9][N:8]([C:11]([CH3:22])([CH3:21])[CH:12]([CH:14]2[CH2:18][CH2:17][C:16]([CH2:19]O)=[CH:15]2)[OH:13])[C:7](=[O:23])[C:6]=1C1C=CC=CC=1.[C:30]1(C)[CH:35]=CC(S(Cl)(=O)=O)=[CH:32][CH:31]=1.C([BH-](CC)CC)C.[Li+].CC1OCN(C(C)(C)C(C2CCC(=C)C2)O)C(=O)C=1C1C=CC=CC=1.CC1OCN(C(C)(C)C(C2CCC(C)=C2)O)C(=O)C=1C1C=CC=CC=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(OCC)C.O1CCCC1.ClCCl.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.C(OCC)(=O)C>[CH3:4][C:5]1[O:10][CH2:9][N:8]([C:11]([CH3:21])([CH3:22])[C:12]([CH:14]2[CH2:18][CH2:17][C:16](=[CH2:19])[CH2:15]2)=[O:13])[C:7](=[O:23])[C:6]=1[C:2]1[CH:1]=[CH:32][CH:31]=[CH:30][CH:35]=1

Participants

14

Reactant 7

HCID 73974-Toluenesulfonyl chlorideHCID 22118258HCID 22118258, compoundHCID 22118307HCID 22118307, compoundHCID 22118323HCID 22118323, compoundHCID 23664628LithiumtriethylborohydrideHCID 178418287HCID 178418287, compoundHCID 178506846HCID 178506846, compound

Product 1

HCID 22118341HCID 22118341, compound

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of ethyl lithium (1.4M) in diethyl ether was added to a stirred solution of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-1-(3-hydroxymethyl-cyclopent-2-enyl)-2-methylpropan-1-ol (0.39 g) in tetrahydrofuran below -60° C. under an argon atmosphere. A solution of p-toluenesulphonyl chloride (0.23 g) in tetrahydrofuran was added below -65° C., followed after 0.5 hour by tetrakis(triphenylphosphine)palladium(0) (0.01 g) in tetrahydrofuran added below -60° C. Finally lithium triethylborohydride (1M) in tetrahydrofuran (1.4 ml) was added below -60° C. The mixture was allowed to slowly warm to 20° C. whilst stirring for 3 hours. Ethyl acetate and water were added and the organic phase washed (brine), dried (magnesium sulphate), evaporated and purified by column chromatography eluting with n-hexane/acetone (2:1) to give a mixture of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(3-methylenecyclopentyl)propan-1-ol and 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(3-methylcyclopent-2-en-1-yl)propan-1-ol (0.1 g). To a stirred solution of the above mixture in dichloromethane were added powdered molecular sieve 4A (0.6 g) and pyridinium chlorochromate (0.15 g) at 20° C. After 3 hours, ether was added, the mixture filtered, evaporated and purified by silica gel column chromatography eluting with n-hexane/diethyl ether (2:1) to give 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methyl-1-(3-methylenecyclopentyl)propan-1-one (Compound 1076, 25 mg), NMR: 1.44(s,6H), 1.94(s,3H), 1.85-2.60(6H), 3.32(1H), 4.84(s,1H), 5.27(s,2H), 7.22-7.40(5H).

Workup

  1. additionadded below -60° C
  2. washthe organic phase washed (brine)
  3. dry with materialdried (magnesium sulphate)
  4. customevaporated
  5. custompurified by column chromatography
  6. washeluting with n-hexane/acetone (2:1)
  7. customto give
  8. customat 20° C
  9. waitAfter 3 hours
  10. filtrationthe mixture filtered
  11. customevaporated
  12. custompurified by silica gel column chromatography
  13. washeluting with n-hexane/diethyl ether (2:1)

Sources & evidence

ORD record
ord-5a3238a4827f429e97c798b45b258fc7
Source dataset
uspto-grants-2000_12
Patent number
US06159902

Reaction notes

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