Hydrochloric Acid → 2-[3-(Tetrahydropyran-2-yloxy)-1-octynyl]-5-oxocyclopentaneheptanoic acid methyl ester

HRID 1834663Notes

Reaction equation

HRID 1834663 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[O:12][CH:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:14]#[CH:15].C#C[CH:23]([OH:29])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].O1C=CCCC1.Cl.[Cl-].[Al+3].[Cl-].[Cl-].[C:41]([O:44][CH2:45]C)(=[O:43])[CH3:42].C1C=CC=CC=1>C1(C)C=CC=CC=1.[NH4+].[Cl-]>[CH3:45][O:44][C:41](=[O:43])[CH2:42][CH2:4][CH2:3][CH2:2][CH2:1][CH2:28][CH:27]1[C:23](=[O:29])[CH2:24][CH2:25][CH:26]1[C:15]#[C:14][CH:13]([O:12][CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][O:6]1)[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 80803,4-dihydro-2H-pyranHCID 131661-Octyn-3-olHCID 6451240Aluminum(III) ChlorideHCID 117890622H-Pyran, 2-[(1-ethynylhexyl)oxy]tetrahydro-HCID 21583983Benzene ethyl acetateHCID 178418339Butyllithium

Product 1

HCID 544292072-[3-(Tetrahydropyran-2-yloxy)-1-octynyl]-5-oxocyclopentaneheptanoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Under a nitrogen atmosphere at -25° C, a solution of butyl lithium (50 ml of 2.2 molar solution in hexane) is added to a solution of 3-(tetrahydropyran-2-yloxy)-1-octyne {21.0 g, readily prepared from 1-octyn-3-ol (E. Crundwell, et al., J. Med. Chem., 8, 41 (1965)) and dihydropyran in the presence of conc. HCl} in toluene (25 ml). The mixture is stirred for 15 minutes and aluminum chloride (4.46 g) is added. After the reaction mixture has been stirred for an additional 45 minutes at -20° C, 5-oxo-1-cyclopentane-1-heptanoic acid methyl ester (11.2 g), described by J. Bagli and T. Bogri, Tetrahedron Letters, 3815 (1972) and U.S. Pat. No. 3,773,795, issued November 20, 1973, is added and the resultant mixture is allowed to come to room temperature (20°-25° C). The mixture is stirred for 16 hr. then diluted with saturated NH4Cl and extracted with ether. The ether extract is washed with saturated NH4Cl, water, dried and concentrated to yield an oily residue. Chromatography of the residue on silica gel using ethyl acetate-benzene (1:9) as eluant affords 2-[3-(tetrahydropyran-2-yloxy)-1-octynyl]-5-oxocyclopentaneheptanoic acid methyl ester (6; R1 = CH3 and R4 = tetrahydropyran-2-yl).

Workup

  1. stirringAfter the reaction mixture has been stirred for an additional 45 minutes at -20° C
  2. additionis added
  3. customto come to room temperature
  4. custom(20°-25° C)
  5. stirringThe mixture is stirred for 16 hr
  6. extractionextracted with ether
  7. extractionThe ether extract
  8. washis washed with saturated NH4Cl, water
  9. customdried
  10. concentrationconcentrated
  11. customto yield an oily residue

Sources & evidence

ORD record
ord-a6a2e7d315b741d483f064819ffb5672
Source dataset
uspto-grants-1978_01
Patent number
US04070482

Reaction notes

Loading…