Water → Temsirolimus

HRID 406967

Reaction equation

HRID 406967 reaction equation
[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:64][CH3:65])[C:8]([CH3:63])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:62])[CH2:15][C@@H:16]([CH3:61])[C:17]([C@H:19]([O:59][CH3:60])[C@H:20]([OH:58])[C:21]([CH3:57])=[CH:22][C@@H:23]([CH3:56])[C:24]([CH2:26][C@@H:27]([C@@H:44]([CH2:46][C@H:47]3[CH2:52][C@@H:51]([O:53][CH3:54])[C@H:50]([OH:55])[CH2:49][CH2:48]3)[CH3:45])[O:28][C:29]([C@H:31]3[N:36]([C:37]([C:39]2=[O:40])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])=[O:25])=[O:18])[CH2:4][CH2:3]1.[CH3:66][C:67]1([C:85](O)=[O:86])[CH2:72][O:71]C(C2C=CC=CC=2)(C2C=CC=CC=2)[O:69][CH2:68]1.S(=O)(=O)(O)O.O>C1COCC1>[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:64][CH3:65])[C:8]([CH3:63])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:62])[CH2:15][C@@H:16]([CH3:61])[C:17]([C@H:19]([O:59][CH3:60])[C@H:20]([OH:58])[C:21]([CH3:57])=[CH:22][C@@H:23]([CH3:56])[C:24]([CH2:26][C@@H:27]([C@@H:44]([CH2:46][C@H:47]3[CH2:52][C@@H:51]([O:53][CH3:54])[C@H:50]([O:55][C:68]([C:67]([CH2:85][OH:86])([CH2:72][OH:71])[CH3:66])=[O:69])[CH2:49][CH2:48]3)[CH3:45])[O:28][C:29]([C@H:31]3[N:36]([C:37]([C:39]2=[O:40])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])=[O:25])=[O:18])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric Acid2×HCID 5284616SirolimusHCID 529317635-Methyl-2,2-diphenyl-1,3-dioxane-5-carboxylic acid

Product 1

HCID 6918289Temsirolimus

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

(189 mg) of 31-trimethyl silyl-42-ester of rapamycin with 5-methyl-2,2-diphenyl-1,3-dioxane-5-carboxylic acid [IId10] was dissolved in 2.8 ml THF and cooled to 0-5° C. Into the reaction mass 0.52 ml 2N sulphuric acid was added and stirred at 25-30° C. for 24 hrs. Then 2 ml THF and 0.52 ml 2 N sulphuric acid was added and stirred at 25-30° C. for 76 hrs. It was then concentrated on rotavapour, residue was dissolved in 2 ml ethyl acetate, and 2-3 drop perchloric acid (HClO4) diluted with 1 ml water was added. The reaction mixture was stirred at 25-30° C. for 24 hrs and reaction mass was dumped into water, and extracted with ethyl acetate. The layers were separated and washed the organic layer with 10% sodium bicarbonate solution and then water. It was dried over sodium sulfate, concentrated on rotavapor to obtain yellow colored oily compound.

Workup

  1. stirringstirred at 25-30° C. for 76 hrs
  2. concentrationIt was then concentrated on rotavapour, residue
  3. dissolutionwas dissolved in 2 ml ethyl acetate
  4. addition2-3 drop perchloric acid (HClO4) diluted with 1 ml water
  5. additionwas added
  6. stirringThe reaction mixture was stirred at 25-30° C. for 24 hrs
  7. customreaction mass
  8. extractionextracted with ethyl acetate
  9. customThe layers were separated
  10. washwashed the organic layer with 10% sodium bicarbonate solution
  11. dry with materialIt was dried over sodium sulfate
  12. concentrationconcentrated on rotavapor
  13. customto obtain yellow colored oily compound

Sources & evidence

ORD record
ord-1b08d1152dc2441b8cdd805ff4f653f5
Source dataset
uspto-grants-2014_06
Patent number
US08754207B2

Linked notes

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