Tetrahydrofuran → 3-Hydroxy-3-[4-(spiro[5.5]undec-1-en-2-ylmethoxy)-phenyl]-propionic acid ethyl ester

HRID 2070585Notes

Reaction equation

HRID 2070585 reaction equation
CCCCCCC.[O:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.C(C1C=CC=CC=1)C.C([N-]C(C)C)(C)C.[Li+].[CH:29]1[C:34]2([CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[CH2:33][CH2:32][CH2:31][C:30]=1[CH2:40][O:41][C:42]1[CH:49]=[CH:48][C:45]([CH:46]=[O:47])=[CH:44][CH:43]=1.[Cl-].[NH4+].[O:52]1CCCC1>C(OCC)(=O)C>[CH2:9]([O:8][C:12](=[O:52])[CH2:11][CH:46]([OH:47])[C:45]1[CH:48]=[CH:49][C:42]([O:41][CH2:40][C:30]2[CH2:31][CH2:32][CH2:33][C:34]3([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]3)[CH:29]=2)=[CH:43][CH:44]=1)[CH3:10]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 57771420HCID 57771420, compound

Product 1

HCID 577714753-Hydroxy-3-[4-(spiro[5.5]undec-1-en-2-ylmethoxy)-phenyl]-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl acetate (2.2 mL) in tetrahydrofuran (100 mL) was added dropwise a 2M heptane/tetrahydrofuran/ethylbenzene solution of lithium diisopropylamide (11.25 mL) at −78° C. under argon atmosphere over 15 minutes, followed by stirring the reaction mixture at −78° C. for 30 minutes. Then, to the reaction mixture was added dropwise a solution of 4-(spiro[5.5]undec-1-en-2-ylmethoxy)-benzaldehyde (4.27 g) obtained in Step 6 in tetrahydrofuran (15 mL) over 10 minutes, followed by stirring the reaction mixture at −78° C. for 40 minutes. After the temperature was raised to room temperature, saturated aqueous ammonium chloride solution (100 mL) was added carefully to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:4 to 1:3) to give 3-hydroxy-3-[4-(spiro[5.5]undec-1-en-2-ylmethoxy)-phenyl]-propionic acid ethyl ester (4.98 g).

Workup

  1. stirringby stirring the reaction mixture at −78° C. for 40 minutes
  2. temperatureAfter the temperature was raised to room temperature
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:4 to 1:3)

Sources & evidence

ORD record
ord-7b4ff39d9f5b4f08b168d667bfbe44c9
Source dataset
uspto-grants-2012_10
Patent number
US08299296B2

Reaction notes

Loading…