Boron tribromide → (2R)-11-(3,17beta-dihydroxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid

HRID 460488Notes

Reaction equation

HRID 460488 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:17]([CH2:18][CH2:19][C@:3]12[CH3:4])[C:16]1[CH:15]=[CH:14][C:13]([O:20]C)=[CH:12][C:11]=1[CH2:10][C@H:9]3[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C@H:31]([CH2:35][CH2:36][C:37]([F:49])([F:48])[C:38]([F:47])([F:46])[C:39]([F:45])([F:44])[C:40]([F:43])([F:42])[F:41])[C:32]([OH:34])=[O:33].B(Br)(Br)Br>ClCCl>[OH:20][C:13]1[CH:14]=[CH:15][C:16]2[C@@H:17]3[C@H:8]([C@H:5]4[C@@:3]([CH2:19][CH2:18]3)([CH3:4])[C@@H:2]([OH:1])[CH2:7][CH2:6]4)[C@H:9]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C@H:31]([CH2:35][CH2:36][C:37]([F:48])([F:49])[C:38]([F:46])([F:47])[C:39]([F:44])([F:45])[C:40]([F:41])([F:42])[F:43])[C:32]([OH:34])=[O:33])[CH2:10][C:11]=2[CH:12]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 86588539(2R)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid

Product 1

HCID 86588538(2R)-11-(3,17beta-dihydroxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acidYield 65.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Anhydrous dichloromethane (10 ml) was added to (2R)-11-(17β-hydroxy-3-methoxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid (358 mg, 0.50 mmol) under nitrogen atmosphere and the resulting mixture was cooled to −78° C. Boron tribromide (1.0 M in tetrahydrofuran, 3.0 ml, 3.0 mmol) was added dropwise to the mixture, which was then stirred on ice for 2.5 hours. The reaction mixture was cooled again to −78° C. and quenched with saturated aqueous sodium bicarbonate over 1 hour. After the reaction mixture was extracted with ethyl acetate, the organic layer was washed sequentially with saturated aqueous potassium bisulfate, saturated aqueous sodium chloride, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure using an evaporator and the resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=4/6) to give (2R)-11-(3,17β-dihydroxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid (231 mg, Yield 60%) as a yellow amorphous mass.

Workup

  1. temperatureThe reaction mixture was cooled again to −78° C.
  2. customquenched with saturated aqueous sodium bicarbonate over 1 hour
  3. extractionAfter the reaction mixture was extracted with ethyl acetate
  4. washthe organic layer was washed sequentially with saturated aqueous potassium bisulfate, saturated aqueous sodium chloride, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customan evaporator
  9. customthe resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=4/6)

Sources & evidence

ORD record
ord-e0b5de9aac044bcea3a72af38d9904c7
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Reaction notes

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