Reacción #1269811

Ecuación de reacción

NH4Cl

methyl 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynoate

Isopropylmagnesium chloride

N,N,N′,N′-tetramethylethylenediamine

→

methyl 4-methyl-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-2-pentenoate

Rendimiento 85.0%

Disolventes

THF

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas obtained
2. 2
   Temperaturacooled to about −70° C., upon which a green suspension
3. 3
   Otrowas formed
4. 4
   workup.STIRRINGThe mixture was stirred at about −70° C. for about 1 h
5. 5
   workup.ADDITIONwas added
6. 6
   OtroThe organic layer was separated
7. 7
   Extracciónthe aqueous layer was extracted with hexanes/ether, approximately 5:1
8. 8
   LavadoThe combined organic extracts were thoroughly washed with saturated NH4Cl solution until no blue color
9. 9
   ExtracciónThe organic extract
10. 10
    Otrowas dried
11. 11
    Concentraciónconcentrated

Procedimiento

Freshly purchased copper iodide (CuI, approximately 1.97 g, approximately 12.2 mmol) was placed under N2 in a four-neck flask. Dry tetrahydrofuran (THF) (about 35 ml) was added, followed by N,N,N′,N′-tetramethylethylenediamine (about 2.76 ml). The mixture was stirred at room temperature until a green-yellow solution was obtained and then cooled to about −70° C., upon which a green suspension was formed. Isopropylmagnesium chloride solution (approximately 12.3 mmol; about 6.1 ml of approximately 2.0 M in tetrahydrofuran (THF) was added slowly, whereupon a green suspension became colorless then turned brown. The mixture was stirred at about −70° C. for about 1 h, then methyl 5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynoate (approximately 1.3 g, approximately 6.1 mmol) dissolved in dry THF (about 5-10 ml) was added. The resultant mixture was stirred at about −70° C. for about 3 h and quickly poured into an ice-cold mixture of saturated NH4Cl and hexanes/ether, approximately 5:1. The organic layer was separated, and the aqueous layer was extracted with hexanes/ether, approximately 5:1. The combined organic extracts were thoroughly washed with saturated NH4Cl solution until no blue color was seen. The organic extract was dried and concentrated. Flash chromatography with hexanes/ethyl acetate, approximately 5:1, afforded methyl 4-methyl-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-2-pentenoate (approximately 1.3 g, approximately 85%) as an approximately 92:8 mixture of E and Z isomers as judged from GC-MS analysis. GC-MS (E isomer, m/z, relative intensity): 172 (2), 171 (3), 155 (32), 142 (8), 141 (6), 139 (6), 95 (17), 85 (100), 67 (16), 57 (10), 55 (11), 43 (11), 41 (16). GC-MS (Z isomer, m/z, relative intensity): 172 (4), 155 (3), 154 (8), 142 (8), 141 (2), 139 (4), 123 (6), 95 (23), 85 (100), 67 (17), 57 (10), 55 (12), 43 (11), 41 (17). 1H NMR (400 MHz, C6D6, δ): 0.86 (d, J=8.0 Hz, E isomer), 0.86 (d, J=8.0 Hz, Z isomer), 1.20-1.42 (m, 4H), 1.55-1.62 (m, 2H), 1.70-1.82 (m, 1H), 2.18-2.31 (m, 1H), 3.02-3.18 (m, 2H), 3.41 (s, OCH3), 3.67-3.73 (m, 1H), 3.81-3.88 (m, 1H), 4.04-4.11 (m, 1H), 4.39 (septet, J=8.0 Hz, H-4, Z isomer), 4.52 (t, J=4.0 Hz, OCHO, Z isomer), 4.66 (t, J=4.0 Hz, OCHO, E isomer), 5.83 (br. s, H-2, E isomer), 5.86 (br. s, H-2, Z isomer). 13C NMR (101 MHz, C6D6, δ, E isomer): 20.0, 21.7 (two carbons), 26.3, 31.4, 32.9, 37.3, 50.9, 61.9, 67.3, 98.8, 115.1, 167.2, 167.8.

Fuente