Water → (5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl ethyl hydrogen phosphate

HRID 720957

Reaction equation

HRID 720957 reaction equation
CC(C)C(O[C@H]1[C@H](OC(=O)C(C)C)[C@@H](COC(=O)C(C)C)O[C@H]([O:25][C:26]2[CH:27]=[CH:28][C:29]3[C:35]4[C:36]([O:44][CH3:45])=[C:37]([O:42][CH3:43])[C:38]([O:40][CH3:41])=[CH:39][C:34]=4[CH2:33][CH2:32][C@H:31]([NH:46][C:47](=[O:49])[CH3:48])[C:30]=3[CH:50]=2)[C@@H]1OC(=O)C(C)C)=O.[P:58](Cl)(Cl)([O:60][CH2:61][CH3:62])=[O:59].[OH2:65]>C1COCC1>[P:58]([OH:65])([O:60][CH2:61][CH3:62])([O:25][C:26]1[CH:27]=[CH:28][C:29]2[C:35]3[C:36]([O:44][CH3:45])=[C:37]([O:42][CH3:43])[C:38]([O:40][CH3:41])=[CH:39][C:34]=3[CH2:33][CH2:32][C@H:31]([NH:46][C:47](=[O:49])[CH3:48])[C:30]=2[CH:50]=1)=[O:59]

Participants

5

Reactant 3

HCID 962WaterHCID 15158Ethyl dichlorophosphateHCID 69586443(2R,3R,4S,5R,6R)-2-[(5S)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl]oxy-3,5-bis(isobutyryloxy)-6-[(isobutyryloxy)methyl]tetrahydro-2H-pyran-4-yl 2-methylpropanoate

Product 1

HCID 57016720(5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl ethyl hydrogen phosphateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

A solution of N-acetyl-colchicinol (1) (0.36 g; 1.0 mmol) in THF (40 ml) under argon was cooled to 0° C. and treated with a 1.0M solution of lithiumHMDS in THF (1.1 ml; 1.1 mmol). The mixture was stirred at 0° C. for 1 hour and then added in portions over about 2 hours to a solution of ethyl dichlorophosphate (400 μl; 3.3 mmol) in THF (150 ml). The mixture was stirred at ambient temperature for 15 minutes. After addition of water (200 ml) the THF was removed by evaporation. After removal of the insoluble material by filtration, the filtrate was purified on HP20 SS resin eluting with a gradient of 0–60% methanol/water. The appropriate fractions were freeze-dried to give (5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl ethyl hydrogen phosphate as a white solid (259 mg).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 15 minutes
  2. customwas removed by evaporation
  3. customAfter removal of the insoluble material
  4. filtrationby filtration
  5. customthe filtrate was purified on HP20 SS resin
  6. washeluting with a gradient of 0–60% methanol/water
  7. customThe appropriate fractions were freeze-dried

Sources & evidence

ORD record
ord-95ada7e48d904c2f8cc910dd1ef46d62
Source dataset
uspto-grants-2006_11
Patent number
US07135502B1

Linked notes

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