1-(3-chlorophenoxy)-3-dimethoxyphosphorylpropan-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process described in Example 1 was repeated, using a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-methoxyiminopropylphosphonate in place of a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-semicarbazonopropylphosphonate, to give dimethyl 3-(3-chlorophenoxy)-2-oxopropylphosphonate, RF = 0.29 (ethyl acetate), RF = 0.58 (5% v/v methanol in methylene dichloride).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process described in Example 1 was repeated, using a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-oximinopropylphosphonate in place of the solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-semicarbazonopropylphosphonate, to give dimethyl 3-(3-chlorophenoxy)-2-oxopropylphosphonate, RF = 0.29 (ethyl acetate), RF = 0.58 (5% v/v methanol in methylene dichloride).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphonate 11 (20.5 g, 70.0 mmol), 2.6 g (62 mmol) of LiCl, and 200 mL of THF were mixed together at 0° C. and 6.10 g (60.4 mmol) of NEt3 was added. Aldehyde 12 (14.0 g, 51.1 mmol) dissolved in 50 mL of CH2Cl2 was then added dropwise. After 1 h, the reaction was poured into 200 mL of a 1/1 mixture of saturated NH4Cl/ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). Combined organic layers were dried over MgSO4, filtered, concentrated, and the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2, to afford 16.2 g (72%) of 13 as a white crystalline solid, m.p.=101.0-102.0° C. 1H NMR δ 8.0-7.9 (m, 2 H), 7.62-7.52 (m, 1 H), 7.50-7.38 (m, 2 H), 7.18 (t, J=8.2 Hz, 1 H), 7.0-6.82 (m, 3 H), 6.75-6.70 (m, 1 H), 6.54 (d, J=15.1 Hz, 1 H), 5.32 (q, J=6.2 Hz, 1 H), 5.12-5.05 (m, 1 H), 4.66 (s, 2 H), 3.0-2.8 (m, 3 H), 2.7-2.2 (m, 3 H). was then added dropwise the layers were separated the aqueous layer was extracted with ethyl acetate (2×100 mL) Combined organic layers were dried over MgSO4 filtered concentrated the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosphonate 11 (20.5 g, 70.0 mmol), 2.6 g (62 mmol) of LiCl, and 200 mL of THF were mixed together at 0° C. and 6.10 g (60.4 mmol) of NEt3 was added. Aldehyde 12 (14.0 g, 51.1 mmol) dissolved in 50 mL of CH2Cl2 was then added dropwise. After 1 h, the reaction was poured into 200 mL of a 1/1 mixture of saturated NH4Cl/ethyl acetate, the layers were separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). Combined organic layers were dried over MgSO4, filtered, concentrated, and the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2, to afford 16.2 g (72%) of 13 as a white crystalline solid, m.p.=101.0-102.0° C. 1H NMR δ 8.0-7.9 (m, 2 H), 7.62-7.52 (m, 1 H), 7.50-7.38 (m, 2 H), 7.18 (t, J=8.2 Hz, 1 H), 7.0-6.82 (m, 3 H), 6.75-6.70 (m, 1 H), 6.54 (d, J=15.1 Hz, 1 H), 5.32 (q, J=6.2 Hz, 1 H), 5.12-5.05 (m, 1 H), 4.66 (s, 2 H), 3.0-2.8 (m, 3 H), 2.7-2.2 (m, 3 H). was then added dropwise the layers were separated the aqueous layer was extracted with ethyl acetate (2×100 mL) Combined organic layers were dried over MgSO4 filtered concentrated the residue was chromatographed on silica gel eluting with ethyl acetate/hexanes, 3/2

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 20.6 g (166 mmol, 238 mol %) of dimethyl methylphosphonate in 110 mL of THF at −78° C. was added dropwise 65 mL (162 mmol, 232 mol %) of a 2.5M solution of n-BuLi in hexanes. After addition was complete, the mixture was stirred for an additional 1 h, after which 15.0 g (69.9 mmol) of aryloxyester 10 in 40 mL of THF was added dropwise. The reaction was stirred for 1 h and then quenched by the addition of 100 mL of saturated NH4Cl. The mixture was poured into 200 mL of a 1/1 mixture of saturated NaCl/ethyl acetate, layers were separated, and the aqueous layer was further extracted with ethyl acetate (2×100 mL). Combined organic layers were dried over MgSO4, filtered, and concentrated, to afford 20.5 g (100%) of 11 as a viscous oil. 1H NMR δ 7.22 (t, J=8.1 Hz, 1 H), 7.05-6.90 (m, 2 H), 6.85-6.78 (m, 1 H), 4.72 (s, 2 H), 3.84 (s, 3 H), 3.78 (s, 3 H), 3.27 (d, J=22.8 Hz, 2 H). After addition The reaction was stirred for 1 h quenched by the addition of 100 mL of saturated NH4Cl The mixture was poured into 200 mL of a 1/1 mixture of saturated NaCl/ethyl acetate, layers were separated the aqueous layer was further extracted with ethyl acetate (2×100 mL) Combined organic layers were dried over MgSO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process described in Example 1 was repeated, using a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-methoxyiminopropylphosphonate in place of a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-semicarbazonopropylphosphonate, to give dimethyl 3-(3-chlorophenoxy)-2-oxopropylphosphonate, RF = 0.29 (ethyl acetate), RF = 0.58 (5% v/v methanol in methylene dichloride).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process described in Example 1 was repeated, using a solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-oximinopropylphosphonate in place of the solution in toluene of dimethyl 3-(3-chlorophenoxy)-2-semicarbazonopropylphosphonate, to give dimethyl 3-(3-chlorophenoxy)-2-oxopropylphosphonate, RF = 0.29 (ethyl acetate), RF = 0.58 (5% v/v methanol in methylene dichloride).