Hexylene Glycol → Temsirolimus

HRID 1437795

Reaction equation

HRID 1437795 reaction equation
[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:72][CH3:73])[C:8]([CH3:71])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:70])[CH2:15][C@@H:16]([CH3:69])[C:17]([C@H:19]([O:67][CH3:68])[C@H:20]([OH:66])[C:21]([CH3:65])=[CH:22][C@@H:23]([CH3:64])[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:56]([C:58]([CH2:62][OH:63])([CH2:60][OH:61])[CH3:59])=[O:57])[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.B([O-])[O-].CC(O)(CC(O)C)C>C(OCC)C>[CH3:1][C@H:2]1[C@@:41]2([OH:43])[O:42][C@H:5]([CH2:6][C@H:7]([O:72][CH3:73])[C:8]([CH3:71])=[CH:9][CH:10]=[CH:11][CH:12]=[CH:13][C@@H:14]([CH3:70])[CH2:15][C@@H:16]([CH3:69])[C:17]([C@H:19]([O:67][CH3:68])[C@H:20]([OH:66])[C:21]([CH3:65])=[CH:22][C@@H:23]([CH3:64])[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:56]([C:58]([CH2:60][OH:61])([CH2:62][OH:63])[CH3:59])=[O:57])[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

4

Reactant 2

HCID 7870Hexylene GlycolHCID 178496632HCID 178496632, compound

Product 1

HCID 6918289TemsirolimusYield 94.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
35 °C

Procedure

In a 3-L multi-neck round-bottomed flask equipped with mechanical stirrer, thermometer, 500-mL pressure equalizing addition funnel, and reflux condenser with a nitrogen head, was added 199 g (0.178 moles) of CCI-779 boronate, a solution of 105 g of 2-methyl-2,4-pentanediol (0.891 moles) in 371 g of diethyl ether and 185 g of heptanes. The mixture was heated to 33-37° C. with stirring under nitrogen and held for 12 h. HPLC showed the consumption of starting CCI-779 boronate (<3%) and phenylboronic acid in the reaction mixture below the specification of less than 3.0% or less than 1.5%. Cooled the reaction mixture to 20-25° C. over a 20 minutes, added 928 g of heptanes through the addition funnel over 1 h, then stirred at 20-25° C. for 1 h. The resulting mixture was filtered on a Buchner funnel. The filtered solids were washed with two portions of 500 mL of heptanes. After drying by suction until essentially no more filtrate is collected, 174 grams of crude CCI-779 was isolated [Strength=93.8%, total impurities=1.36%, rapamycin=0.40% (HPLC); ether=0.15%, heptanes=0.26% (GC)].

Workup

  1. customIn a 3-L multi-neck round-bottomed flask equipped with mechanical stirrer
  2. additionaddition funnel
  3. temperaturereflux condenser with a nitrogen head
  4. customthe consumption of starting CCI-779 boronate (<3%) and phenylboronic acid in the reaction mixture below the specification of less than 3.0% or less than 1.5%
  5. temperatureCooled the reaction mixture to 20-25° C. over a 20 minutes
  6. additionadded 928 g of heptanes through the addition funnel over 1 h
  7. stirringstirred at 20-25° C. for 1 h
  8. filtrationThe resulting mixture was filtered on a Buchner funnel
  9. washThe filtered solids were washed with two portions of 500 mL of heptanes
  10. customAfter drying by suction until essentially no more filtrate
  11. customis collected

Sources & evidence

ORD record
ord-e981509dbc444e009baae1c5a130788a
Source dataset
uspto-grants-2009_11
Patent number
US07622578B2

Linked notes

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