3,4-dihydro-2H-pyran → Methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate

HRID 1182627Notes

Reaction equation

HRID 1182627 reaction equation
O1CCCC[CH:2]1[O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.[CH2:14](O)[CH2:15][C:16]#C.C1(C)C=CC(S(O)(=O)=[O:26])=CC=1.N1C=CC=CC=1.O1C=CCCC1>C(Cl)Cl.O>[OH:9][CH2:10][CH2:11]/[C:12](/[CH:15]([CH3:16])[CH3:14])=[CH:13]\[C:8]([O:7][CH3:2])=[O:26]

Participants

7

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 135663-Butyn-1-OL2×HCID 161440Pyridine 4-methylbenzene-1-sulfonateHCID 263182Tetrahydropyranyl ether

Product 1

HCID 71624430Methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate was synthesized according to scheme shown in FIG. 1. Unless otherwise specified all reagents and solvents were purchased from Aldrich Chemical Co. Tetrahydropyranyl ether (THP) protection of 3-butyn-1-ol was conducted following a procedure by Rama Rao et al. (1986). A solution of 3-butyn-1-ol (approximately 14.0 g, approximately 0.2 mol) in methylene chloride (approximately 75 ml, dried by distillation from CaH2) was placed in a flask under N2. The mixture was cooled to approximately 0° C., and pyridine p-toluenesulfonate (approximately 0.28 g) was added. 3,4-Dihydro-2H-pyran (about 20.1 ml) was added via a dropping funnel maintaining the temperature between approximately 0 and approximately 5° C. The mixture was stirred at this temperature for about 1 h, then warmed to about 25° C. and stirred for additional about 2 h. Thin layer chromatography (silica gel, hexanes/ethyl acetate, approximately 3:1) showed that the reaction was complete. The reaction mixture was taken into cold water (approximately 70 ml) and transferred to a separatory funnel. The layers were separated and the aqueous phase was extracted with methylene chloride. Combined organic extracts were washed with NaHCO3 (aq), brine, and dried with Na2SO4 (anhydrous). Distillation produced approximately 23 g of THPO-protected 3-butyn-1-ol with a by of about 50-55° C./4 mm Hg with GC-MS (m/z, relative intensity): 153 (2, M+-1), 99 (9), 85 (100), 79 (9), 67 (20), 53 (42), 41 (33). The mass spectrum matched the spectrum presented in the NIST MS library for this intermediate compound.

Workup

  1. temperaturemaintaining the temperature between approximately 0 and approximately 5° C
  2. temperaturewarmed to about 25° C.
  3. stirringstirred for additional about 2 h
  4. customtransferred to a separatory funnel
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with methylene chloride
  7. washCombined organic extracts were washed with NaHCO3 (aq), brine
  8. dry with materialdried with Na2SO4 (anhydrous)
  9. distillationDistillation
  10. customproduced approximately 23 g of THPO-protected 3-butyn-1-ol with a by of about 50-55° C./4 mm Hg with GC-MS (m/z, relative intensity)

Sources & evidence

ORD record
ord-3836beaa1ecd436c9444c57d2330e7bf
Source dataset
uspto-grants-2014_03
Patent number
US08663621B2

Reaction notes

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