Tetrahydrofuran → HCID 22399013, compound

HRID 846353Notes

Reaction equation

HRID 846353 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:10]([C:12]([O:14]C(OCC)C)=[O:13])[OH:11])=O)([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].CS(Cl)(=O)=O.[CH2:43]1[CH2:47][O:46][CH2:45][CH2:44]1>CCCCCC.C(OCC)(=O)C>[C:1]([O:5][C:6]1[O:13][C:12](=[O:14])[CH:10]([O:11][CH:45]([O:46][CH2:47][CH3:43])[CH3:44])[C:9]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:8]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 31297Methanesulfonyl chlorideHCID 23665647Potassium tert-butoxideHCID 67743817HCID 67743817, compound

Product 1

HCID 22399013HCID 22399013, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 497 mg (1.16 mmol) of N-tertbutoxycarbonyl-O-(1-ethoxyethyl)-3,3-diphenylisoserine (3) in 20 mL of THF is added 261 mg (2.33 mmol) of solid potassium tert-butoxide and the mixture is stirred at 25° C. for 30 min. A solution of 134 mg (1.16 mmol) of methanesulfonyl chloride in 3.2 mL of THF is added and the mixture is stirred at 25° C. for 1.5 hour. The mixture is diluted with 80 mL of hexane and ethyl acetate, and this solution is extracted with 20 mL of saturated aqueous sodium bicarbonate solution and 10 mL of brine. The organic phase is dried over sodium sulfate and concentrated to give 243 mg (59%) of 2-tertbutoxy-4,4-diphenyl-5-(1-ethoxyethoxy)-4,5-dihydro-1,3-oxazin-6-one as a colorless oil. N-debenzoykl-N-tertbutoxycarbonyl-3'-phenyl taxol. To a small reaction vessel is added 90 mg (0.218 mmol) of 2-tertbutoxy-4,4-diphenyl-5-(1-ethoxyethoxy)-4,5-dihydro-1,3-oxazin-6-one, 40 mg (0.057 mmol) of 7-O-triethylsilyl baccatin III, 6.9 mg (0.057 mmol) of 4-dimethylamino pyridine (DMAP), and 0.029 mL of pyridine. The mixture is stirred at 25° C. for 12 hours and diluted with 100 mL of ethyl acetate. The ethyl acetate solution is extracted with 20 mL of 10% aqueous copper sulfate solution, dried over sodium sulfate and concentrated. The residue is filtered through a plug of silica gel eluted with ethyl acetate. Flash chromatography on silica gel eluted with ethyl acetate/hexane followed by recrystallization from ethyl acetate/hexane gives 44 mg (66%) of N-debenzoyl-N-tertbutoxycarbonyl-2 -(1-ethoxyethyl)3'-phenyl-7-O-triethylsilyl taxol as a ca 3:1 mixture of diastereomers

Workup

  1. stirringthe mixture is stirred at 25° C. for 1.5 hour
  2. extractionthis solution is extracted with 20 mL of saturated aqueous sodium bicarbonate solution and 10 mL of brine
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-2ddfd420f14145769a4dde93b725830a
Source dataset
uspto-grants-1992_08
Patent number
US05136060

Reaction notes

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