| 100% |
|
The NaH (60% mineral oil suspension, 33.3g, 832 . 38mmol) THF suspended water-free (1L) in, in 0 C lower, added to the 1,4-dioxaspiro [4.5] decane-8-one (100g, 640.29mmol) anhydrous THF (500 ml) solution, 1-hour internal dropping end. Furthermore, at -20 C lower, the phosphoryl acetic acid triethyl ester (203.23g, 832 . 38mmol) is dripped into the in the above-mentioned suspension system, 1-hour internal dropping end. The resulting system is moved to the room temperature, is continuously stirred for 2 hours, then water (1L) quenching the reaction, and using ethyl acetate (1Lx3) extraction. Combined with the phase, saturated salt water for (1L) washing, anhydrous Na2SO4drying, concentrated filtrate under reduced pressure, the resulting residue by a silica gel column chromatography (PE/EtOAc = 10/1 (v/v)) purification, to obtain the title compound as of bombycinous (157g, 100%). |
| 100% |
|
Step 1) ethyl 2-(l ,4-dioxaspiror4.51decan-8-ylidene)acetate [0350] To a suspension of NaH (60% mineral oil suspension, 33.3 g, 832.38 mmol) in anhydrous THF (1 L) was added a solution of l ,4-dioxaspiro[4.5]decan-8-one (100 g, 640.29 mmol) in anhydrous THF (500 mL) dropwise at 0 C for 1 h and the reaction mixture was stirred for another 1 h. Then, triethyl phosphonoacetate was added dropwise to the above suspension at -20 C in 1 h. The resulting mixture was allowed to warm to rt, and stirred for another 2 h, then quenched with 0 (1 L) and extracted with EtOAc (1 L x 3). The combined organic phases were washed with brine (1 L), then dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v) = 1/10) to give the title compound as pale yellow oil (157 g, 100 %). NMPv (600 MHz, CDCb): δ (ppm) 5.64 (s, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.95 (s, 4H), 2.97 (m, 2H), 2.36 (m, 2H), 1.74 (m, 4H), 1.25 (t, J= 7.2 Hz, 4H). |
| 100% |
|
To a suspension of NaH (60% suspension in oil) (1.42 g, 35.45 mmol) in THF (190mL) at 0 C, under N2, ethyl 2-(diethoxyphosphoryl)acetate (7 mL, 35.45 mmol) was addeddrop-wise. The mixture was stirred for 30’, then 1,4-dioxaspiro[4.5]decan-8-one (5g, 32 mmol)in THF (20 mL) was added drop-wise. The resulting mixture was stirred at RT for 2 hrs and thenconcentrated under vacuum. The residue was taken up with Et20, washed with water and Brine, dried over Na2SO4 and concentrated to obtain 7.58 g of title compound (p121, y= quant) as colourless oil. MS (m/z): 227.2 [IVIH]t |
| 100% |
With sodium hydride; In tetrahydrofuran; mineral oil; at -20 - 20℃; for 2h; |
NaH (60% suspended in mineral oil, 33.3 g, 832.38 mmol) was suspended in dry THF (1 L), and then the suspension was placed at 0 C, 1,4-dioxaspiro[4.5]decan-8-one (100 g, 640.29 mmol) in dry THF (500 mL) dropwise over 1 hour to give a suspension. Then, triethyl phosphonoacetate (203.23 g, 832.38 mmol) was added dropwise to the above suspension at -20 C, and the mixture was dropwise added in 1 hour to obtain a reaction system. The resulting reaction was moved to room temperature and stirring continued for 2 hours, then the reaction was quenched with water (1 L) and extracted with ethyl acetate (1 L x 3). The combined organic phases were washed with brine (1 L), then dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (PE / EtOAc (v / v) = 10/1) to give the title compound as a pale yellow oil (157 g, 100%). |
| 100% |
With sodium hydride; In tetrahydrofuran; kerosene; at -20 - 20℃; for 4h; |
At 0 C, NaH (60% [w / w], 33.3 g, 832.38 mmol) suspended in kerosene was added to dry tetrahydrofuran (500 mL) and 1,4-dioxaspiro[4.5]decan-8-one (100 g, 640.29 mmol) was added dropwise over 1 hour. Then triethyl phosphonoacetate (172.26 g, 768.35 mmol) was added dropwise at -20 C for 1 hour. The reaction was warmed to room temperature and stirred for 2 hours before it was diluted with water (1 L), extracted with ethyl acetate (1 L × 3), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10/1) to give the title compound as a pale yellow oil (145 g, 100%). |
| 96% |
|
Triethyl phosphonoacetate (21.79 ml, 109 mmol) was added to a suspension of sodium hydride (3.84 g, 96 mmol) in THF (64.0 ml) and 0 C. Reaction was stirred at room temperature for 30 minutes. After 30 minutes, the reaction was recooled to 0 C and a solution of 1,4-dioxaspiro[4.5]decan-8-one (10 g, 64.0 mmol) in 5 mL THF wasadded. The reaction was then stirred at room temperature for 30 minutes prior to quenching with water. The mixture was extracted with DCM three times. Combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. Crude residue was purified via silica gel chromatography to give Intermediate 71A (13.88 g, 61.3 mmol, 96% yield). TLC: product stains as purple spot in anisaldehyde (Rf= 0.75in 1:1 Hex/EtOAc). ‘H NMR (400 MHz, chloroform-d) ö: 5.65 (s, 1H), 4.13 (q, J=7.2 Hz,2H), 3.92-3.99 (m, 4H), 2.94-3.02 (m, 2H), 2.3 1-2.40 (m, 2H), 1.71-1.79 (m, 4H), 1.26 (t, J=7.2 Hz, 3H). |
| 96% |
|
Triethyl phosphonoacetate (21.79 ml, 109 mmol) was added to a suspension of sodium hydride (3.84 g, 96 mmol) in THF (64.0 ml) and 0 C. Reaction was stirred at room temperature for 30 minutes. After 30 minutes, the reaction was recooled to 0 C and a solution of l,4-dioxaspiro[4.5]decan-8-one (10 g, 64.0 mmol) in 5 mL THF was added. The reaction was then stirred at room temperature for 30 minutes prior to quenching with water. The mixture was extracted with DCM three times. Combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. Crude residue was purified via silica gel chromatography to give Intermediate 83A (13.88 g, 61.3 mmol, 96%> yield). TLC: product stains as purple spot in anisaldehyde (Rf = 0.75 in 1 : 1 Hex/EtOAc). 1H NMR (400 MHz, chloroform-d) δ: 5.65 (s, 1H), 4.13 (q, J=7.2 Hz, 2H), 3.92-3.99 (m, 4H), 2.94-3.02 (m, 2H), 2.31-2.40 (m, 2H), 1.71-1.79 (m, 4H), 1.26 (t, J=7.2 Hz, 3H) |
| 96% |
|
Triethyl phosphonoacetate (21.79 ml, 109 mmol) was added to a suspension ofsodium hydride (3.84 g, 96 mmol) in THF (64.0 ml) and 0 C. Reaction was stirred atroom temperature for 30 minutes. After 30 minutes, the reaction was recooled to 0 C and a solution of 1,4-dioxaspiro[4.5]decan-8-one (10 g, 64.0 mmol) in 5 mL THF was added. The reaction was then stirred at room temperature for 30 minutes prior to quenching with water. The mixture was extracted with DCM three times. Combinedorganic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. Crude residue was purified via silica gel chromatography to give Intermediate 305A (13.88 g, 61.3 mmol, 96% yield). TLC: product stains as purple spot in anisaldehyde (Rf = 0.75 in 1:1 Hex/EtOAc). ‘H NMR (400 MHz, chloroform-d) ö: 5.65 (s, 1H), 4.13 (q, J7.2 Hz, 2H), 3.92-3.99 (m, 4H), 2.94-3.02 (m, 2H), 2.3 1-2.40 (m, 2H), 1.7 1-1.79 (m,4H), 1.26 (t, J7.2 Hz, 3H). |
| 96% |
|
[00187] Tri ethyl phosphonoacetate (21.79 ml, 109 mmol) was added to a suspension of sodium hydride (3.84 g, 96 mmol) in THF (64.0 ml) and 0 C. Reaction was stirred at room temperature for 30 minutes. After 30 minutes, the reaction was recooled to 0 C and a soution of l,4-dioxaspiro[4.5]decan-8-one (10 g, 64.0 mmol) in 5 mL THF was added. The reaction was then stirred at room temperature for 30 minutes prior to quenching with water. The mixture was extracted with DCM three times. Combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. Crude residue was purified via silica gel chromatography to give intermeduate 3A (13.88 g, 61.3 mmol, 96 % yield). TLC: product stains as purple spot in anisaldehyde (Rf = 0.75 in 1 : 1 Hex/EtOAc). NMR (400 MHz, CHLOROFORM-d) δ: 5.65 (s, 1H), 4.13 (q, J=7.2 Hz, 2H), 3.92-3.99 (m, 4H), 2.94-3.02 (m, 2H), 2.31 -2.40 (m, 2H), 1.71 -1.79 (m, 4H), 1.26 (t, J=7.2 Hz, 3H) |
| 96% |
|
Triethyl phosphonoacetate (21.79 ml. 109 mmoi) was added to a suspension of sodium hydride (3.84 g, 96 mrnol) in TI-iF (64.0 ml) and 0 C. Reaction was stirred at room temperature for 30 minutes. After 30 minutes, the reaction was recooled to 0 C and a soution of 1,4-dioxaspiro[4.5Idecan-8-one (10 g, 64.0 mmol) in 5 mL THF was added. The reaction was then stirred at room temperature for 30 minutes prior to quenching with water, The mixture was extracted with DCM three times. Combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. Crude residue was purified via silica gel chromatography to give intermediate 13A (13.88 g, 61.3 mmoi, 96 % yield). TLC: product stains as purple spot in anisaldeliyde (RI 0 7 in 11 He [tO’.c) ‘HMR(400 MHz (HLOROH)RNI-d) 5 565 (1H), 4.13 (q, J=7.2 Hz, 2Ff), 3.92-3.99 (m, 4H), 2.94-3.02 (in, 2H), 2.31-2.40 (m, 2H). 1.71-1.79 (in, 4H), 1.26 (t, J=7.2 Hz, 3H) |
| 95% |
|
At 0C, to a suspension of NaH (60% in oil) (6.92 g, 288 mmol) in anhydrous THF (650 ml.) under nitrogen with vigorous stirring was added the triethyl phosphonoacetate (52.5 g, 288 mmol.) dropwise. After stirred at OoC for 30 min, 1 ,4-cyclohexanedione monoethylene ketal (41 g, 260 mmol) in THF (150 ml.) was added dropwise. The resulting mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was poured into saturated aq. NH4CI and extracted with EtOAc. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash chromatography (silica gel, 0-30% EtOAc in PE) to afford the title compound (56 g, 95% yield). (ESI) m/z calcd for CI2HI804: 226.12. Found: 227.33 (M+1 )+. |
| 95% |
|
At 0C, to a suspension of NaH (60% in oil) (6.92 g, 288 mmol) in anhydrous THF (650 mL) under nitrogen with vigorous stirring was added the triethyl phosphonoacetate (52.5 g, 288 mmol.) dropwise. After stirred at 0C for 30 min, 1 ,4-cyclohexanedione monoethylene ketal (41 g, 260 mmol) in THF (150 mL) was added dropwise. The resulting mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was poured into saturated aq. NH4CI and extracted with EtOAc. The organics were washed sequentially with water and brine, and dried over Na2S04. Filtration and concentration in vacuum gave a crude product, which was purified by flash (0170) chromatography (silica gel, 0-30% EtOAc in PE) to afford the title compound (56 g, 95% yield). (ESI) m/z calcd for Ci2Hi804: 226.12. Found: 227.33 (M+1)+. |
| 94% |
|
Step-1: Ethyl 2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate A solution of compound 1 (10.05 g, 64.04 mmol, 1.0 eq.) in THF (30 ml) was added dropwise to a suspension NaH (1.84 g, 76.85 mmol, 1.2 eq.) in THF (90 ml) at 0 C. and the mixture was stirred at same temperature for 1 h. Triethyl phosphonoacetate (16.5 ml, 83.25 mmol, 1.3 eq.) was added to the reaction mixture at -20 C. and the reaction mixture was allowed to warm to RT and stir for 2 h. The reaction mixture was diluted with ethyl acetate (100 ml), washed with water (2*100 ml) and the organic layer dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield compound 2. Yield: 94% (17.28 g, 60.2 mmol). |
| 93% |
|
To a solution of THF (18 mL) under argon was added 0.38 g (47.8 mmol, 5 equiv) of LiH, followed by slow addition of 8.78 G (47.8 mmol, 5 equiv) of triethyl phosphonoacetate. The solution was stirred at rt for 1 h and 1.49 g (9.6 mmol, 1 equiv) of 1, 4-cyclohexanedione mono-ethylene ketal was added and the solution was heated at 65 C for 16 h. Upon cooling the solution was treated with MeOH (10 mL) and water (5 mL) and concentrated in vacuo. The resulting yellow oil was purified by silica gel chromatography eluting with 4: 1 Hex/EtOAc to yield 1.89 g (93%) of a clear oil.'H-NMR (CDCI3-D) 8 5.67 (s, 1H), 4.16 (t, 2H), 3.99 (m, 4H), 3.02 (m, 2H), 2.39 (m, 2H), 1.78 (m, 4H), 1.29 (t, 3H); LCMS RT = 2.56 min; [M+H] + = 226.9. |
| 93% |
|
Example 1; Preparation of ethyl [4-({3-chloro-4-[(3-fluorobenzyl)oxy] phenyl )amino)[1]benzothieno[2,3-d]pyrimidin-7-yl]acetate; Step 1. Preparation of ethyl 1,4-dioxaspiro[4.5]dec-8-ylideneacetate; To a solution of THF (18 mL) under argon was added 0.38 g (47.8 mmol, 5 equiv) of LiH, followed by slow addition of 8.78 g (47.8 mmol, 5 equiv) of triethyl phosphonoacetate. The solution was stirred at rt for 1 h and 1.49 g (9.6 mmol, 1 equiv) of l,4-dioxa-spiro[4.5]decan-8-one was added and the solution was heated at 65C for 16 h. Upon cooling the solution was treated with MeOH (10 mL) and water (5 mL) and concentrated in vacuo. The resulting yellow oil was purified by silica gel chromatography eluting with 4: 1 Hex/EtOAc to yield 1.89 g (93%) of a clear oil. 1H- NMR (CDCl3-d) δ 5.67 (s, 1H), 4.16 (t, 2H), 3.99 (m, 4H), 3.02 (m, 2H), 2.39 (m, 2H), 1.78 (m, 4H), 1.29 (t, 3H); LCMS RT = 2.56 min, [M+H]+ = 226.9. |
| 93% |
|
Triethyl phosphonoacetate (12.2g, 54.4mmol) was dissolved in tetrahydrofuran (100mL), at 0 C was added sodium hydride (1.92g, 48.0mmol), the reaction mixture was stirred under nitrogen atmosphere for 30 minutes.Then at 0 C dissolved in tetrahydrofuran (15mL) 1,4-cyclohexanedione monoethylene ketal (5.00g, 32.0mmol) was added dropwise to the reaction mixture, the reaction solution was stirred at 25 C for 3 hours. Water was added (25mL) to quench the reaction and extracted with dichloromethane (20mLx3). The combined organic phase was washed with saturated brine (20 mL), dried over anhydrousOver sodium sulfate, and concentrated under reduced pressure, the residue was residue was purified by silica gel column chromatography (5: 1 petroleum ether / acetic acidEthyl ester, Rf = 0.3), give ethyl 2-(1,4-dioxa-spiro[4.5]decane-8-ylidene)acetate (6.30g, Colorless oil). Yield: 93%. |
| 90% |
|
A solution of triethyl phosphonoacetate (11 mmol) in THF (50 ml) was added slowly to a suspension, cooled to 0 C., of NaH (10 mmol) in THF (50 ml), and the reaction mixture was stirred for 30 min. 1,4-Dioxa-spiro[4.5]decan-8-one (10 mmol) in THF (50 ml) was then added dropwise at 0 C., and stirring was carried out for 16 h. After addition of ice and aqueous saturated NaCl solution, the aqueous phase was washed with ethyl acetate and the organic phase with water and aqueous saturated NaCl solution. The combined organic phases were dried over Na2SO4 and, after filtration, the solvent was removed in vacuo. The product was purified by column chromatography (20% ethyl acetate/hexane). Yield: 90%. |
| 83% |
With sodium hydride; In tetrahydrofuran; at 0℃; |
Into a 250-mL round-bottom flask, was placed ethyl 2-(diethoxyphosphoryl)acetate (14.4 g, 64.23 mmol, 1 equiv), tetrahydrofuran (150 mL), sodium hydride (5.12 g, 213.33 mmol, 3.33 equiv), l,4-dioxaspiro[4.5]decan-8-one (10 g, 64.03 mmol, 1 equiv). The resulting solution was stirred overnight at 0 C. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3x50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x50 mL of H2O. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 :5). This resulted in 12 g (83%) of as a yellow liquid. Analytical Data: 1H NMR (300 MHz, Chloroform-d) δ 5.67 (p, J= 1.1 Hz, 1H), 4.15 (q, J= 7.1 Hz, 2H), 3.98 (s, 4H), 3.00 (ddd, J= 7.8, 5.1, 1.2 Hz, 2H), 2.44 - 2.32 (m, 2H), 1.84 - 1.70 (m, 4H), 1.28 (t, J= 7.1 Hz, 3H). |
| 69% |
|
To a solution of commercially available ethyl 2-diethoxyphosphorylacetate(9.5 g, 42.3 mmol) in THE (20 mL) was added NaH (1 .7 g, 42.3 mmol) at 0C. The mixture solution was stirred at 0C for 1 h. Then a solution ofcommercially available 1 ,4-dioxaspiro[4.5]decan-8-one (6 g, 38.5 mmol) in THE (5 mL) was added at 000. The solution was stirred at r.t overnight. The mixture was quenched with aqueous NH4CI and extracted with EtOAc, the organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated to give the crude product which was purified by column to givereagent KR-46 (6.6 g, 69 % yield) as a white solid. ESI-MS (Mi-i): 227.2; calc. for C12H1804: 226.1. |
|
|
A solution of triethyl phosphonoacetate (1.1 eq.) in THF (5 ml/mmol) was added slowly to a suspension, at 0 C., of 60% NaH (1 eq.) in dry THF (5 ml/mmol). The resulting reaction mixture was stirred for 30 min at RT. It was then cooled to 0 C., and 1,4-dioxa-spiro[4.5]decan-8-one (1 eq.) in dry THF (5 ml/mmol) was added slowly at a constant temperature. The reaction mixture was stirred for 16 h at 25 C. Quenching with ice and sat. sodium chloride solution was carried out, the aqueous phase was extracted with ethyl acetate, and the organic phase was washed successively with water and sodium chloride solution. The combined org. phases were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (20% ethyl acetate in n-hexane). Yield: 90 |
|
|
(Diethoxy-phosphoryl)-acetic acid ethyl ester (7.05 ml_) was added dropwise to a suspension of NaH (1540 mg, 60% dispersion in mineral oil) in THF (50 ml_) at O 0C. The resulting solution was stirred for 30 minutes at room temperature under inert atmosphere. A solution of 1 ,4-Dioxa- spiro[4.5]decan-8-one (5.0 g) in THF (25 ml_) was then added dropwise and the resulting mixture was stirred at room temperature under inert atmosphere for 4 h. The solvent was evaporated to a minimum volume, water was added and the resulting residue was extracted with 50% Heptane/EtOAc. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford the crude product (7.2 g). 1H NMR (400 MHz, CDCI3) δ ppm 1.25 (t, J=7.22 Hz, 3H), 1.66 - 1.82 (m, 4H), 2.28 - 2.48 (m, 2H), 2.90 - 3.07 (m, 2H), 3.96 (s, 4H), 4.13 (q, J=7.03 Hz, 2H), 5.64 (s, 1 H). MS (ESI, m/z) 227.2 (M+H). |
|
|
PLE 18["4 -( { [( 1 Z)-2-fer/-butyl-2-methyl- 1 -oxido- 1 k5-diazan- 1 -ylidenel amino } oxy)cyclohexyl] acetic acid Step A: ethyl L4-dioxaspiro[4.5]dec-8-ylideneacetate; Triethylphosphonoacetate (63.3mmol5 14.19g) was added to a suspension of NaH (60%) (2.53 g) in THF (100 ml) at 0 C and the mixture was stirred for 30 min at the same temperature. Then, to the mixture was dropped 1 ,4-cyclohexanedione monoetliylene acetal (57.5 mmol, 8.98 g) in THF (30ml) at 0C and stirring was conti ued for lh. After addition of water, the mixture was extracted with Et20. The aqueous layer was extracted with EtOAc and combined organic solution was washed with brine, dried over NaS0 , and concentrated under reduced pressure to provide the title compound. |
|
|
Step 1 : Synthesis of ethyl 2-(l,4-dioxaspiro[4.5]decan-8-yl)acetate. [00395] To a cooled (0C) suspension of NaH (60%, 4.4 g, 110 mmol) in THF (200 mL) was added triethyl phosphonoacetate (25.16 g, 110 mmol) at a rate so as to produce gentle gas evolution. After complete addition, the homogeneous solution was stirred for 30 min. The this solution was added 1 ,4-cyclohexanedione monoethylene ketal (15.62 g, 100 mmol) in THF (40 mL) over 10 min. After complete addition, the ice bath was removed and stirring continued for 3 h. The reaction was quenched by addition of saturated aqueous NH4C1, extracted with EtOAc, washed with brine, dried over Na2S04. Filtration and evaporation to dryness gave the crude product which was used in the next step without further purification. |
|
|
Into a 10L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1,4-dioxaspiro[4.5]decan-8-one 1d (350 g, 2.24 mol, 1.00 equiv) in tetrahydrofuran (3.5 L). This was followed by the addition of sodium hydride (115 g, 2.88 mol, 1.28 equiv, 60%) dropwise with stirring at 0C in 30 min. To this was added ethyl 2- (diethoxyphosphoryl)acetate (517.6 g, 2.31 mol, 1.03 equiv) dropwise with stirring at room temperature in 1 hr. The resulting solution was stirred for 4 h at room temperature. The reaction was then quenched by the addition of 4 L of water. The resulting solution was extracted with 8 L of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 1e. |
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|
To a stirred solution of 10.8 g (48.2 mmol) of ethyl 2-(diethoxyphosphoryl) acetate in 130 mL of THF was added 1 .90 g (79.1 mmol) of NaH (60 % in coal oil) at 0 C under argon atmosphere. The mixture was stirred at 0 C for 1 h. After addition of a solution of 5.0 g (32.0 mmol) of 1 ,4-dioxaspiro[4.5]decan-8-one in THF dropwise at 0 C, the mixture was stirred at 0 C for 30 min and at RT for 5 h, and then quenched with 150 mL NH4CI aqueous solution. The mixture was extracted with three 150 mL portions of ethyl acetate and washed with The filtrate was concentrated to give a residue, which was purified by silica gel column chromatography eluting with 0 to 10 % gradient of ethyl acetate in petroleum ether to afford compound 6-1 . LC-MS: m/e = 227 [M+H]+ |
| 16.252 g |
|
To a stirred solution of NaH (2.82 g, 70.51 mmol) in THF (100 ml) was added ethyl 2- (diethoxyphosphoryl) acetate (15.8 g, 70.51 mmol) at 0 . After the mixture was stirred for 0.5 h at rt and then cooled down to 0. 1, 4-dioxaspiro [4.5] decan-8-one (10 g, 64.1 mmol) was added in portions. After stirring for 0.5 h at rt, ice water was added and extracted with EA. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give 16.252 g of the title product as a yellow oil. |
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