2-ethoxy-2-methylpropanoic acid

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

Procedure: A solution of 2-ethoxy-2-methylpropanoic acid (1.1 g, 8.32 mmol) in MeCN (15 mL) was treated with EDC (1.596 g, 8.32 mmol) and HOBT (1.275 g, 8.32 mmol), stirred at RT for 2 h, treated with NH4OH (˜15M, 1.7 mL, ˜25.5 mmol) and stirred at RT overnight. The mixture was treated with satd. NaHCO3 and water, extracted with EtOAc (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanamide (1.1 g, 101%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 7.03 (s, 2H), 3.31 (q, J=7.0 Hz, 2H), 1.21 (s, 6H), 1.10 (t, J=7.0 Hz, 3H). stirred at RT overnight The mixture was treated with satd NaHCO3 and water, extracted with EtOAc (5×) the combined organics were dried over MgSO4 concentrated to dryness

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

Procedure: A solution of 2-ethoxy-2-methylpropanoic acid (1.1 g, 8.32 mmol) in MeCN (15 mL) was treated with EDC (1.596 g, 8.32 mmol) and HOBT (1.275 g, 8.32 mmol), stirred at RT for 2 h, treated with NH4OH (˜15M, 1.7 mL, ˜25.5 mmol) and stirred at RT overnight. The mixture was treated with satd. NaHCO3 and water, extracted with EtOAc (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanamide (1.1 g, 101%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 7.03 (s, 2H), 3.31 (q, J=7.0 Hz, 2H), 1.21 (s, 6H), 1.10 (t, J=7.0 Hz, 3H). stirred at RT overnight The mixture was treated with satd NaHCO3 and water, extracted with EtOAc (5×) the combined organics were dried over MgSO4 concentrated to dryness

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

Procedure: A solution of methyl 2-ethoxy-2-methylpropanoate (1.6 g, 10.95 mmol) in MeOH (14 mL) was treated drop-wise with a solution of KOH (1.228 g, 21.89 mmol) in water (7 mL) and stirred at RT overnight. The mixture was treated with water, washed with Et2O (2×) and the aqueous layer was acidified to pH 2 with 2M HCl. The mixture was extracted with EtOAc (4×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanoic acid (1.1 g, 76%) as a colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 12.42 (s, 1H), 3.34 (q, J=7.0 Hz, 2H), 1.28 (s, 6H), 1.06 (t, J=7.0 Hz, 3H). washed with Et2O (2×) The mixture was extracted with EtOAc (4×) the combined organics were dried over MgSO4 concentrated to dryness

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

Procedure: A procedure similar to that described in Example 10, above, was followed, but using 1.15 g of 2-ethoxy-2-methylpropionic acid and 1.0 g of (4R,6R)-6-{(1S,2S,6S,8S,8aR)-2-[1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above], to give 414 mg of a fraction containing the title compound. This fraction was usedin the next step without further purification. to give 414 mg of a fraction

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

Procedure: A solution of 2-ethoxy-2-methylpropanoic acid (1.1 g, 8.32 mmol) in MeCN (15 mL) was treated with EDC (1.596 g, 8.32 mmol) and HOBT (1.275 g, 8.32 mmol), stirred at RT for 2 h, treated with NH4OH (˜15M, 1.7 mL, ˜25.5 mmol) and stirred at RT overnight. The mixture was treated with satd. NaHCO3 and water, extracted with EtOAc (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanamide (1.1 g, 101%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ 7.03 (s, 2H), 3.31 (q, J=7.0 Hz, 2H), 1.21 (s, 6H), 1.10 (t, J=7.0 Hz, 3H). stirred at RT overnight The mixture was treated with satd NaHCO3 and water, extracted with EtOAc (5×) the combined organics were dried over MgSO4 concentrated to dryness

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

Procedure: A solution of methyl 2-ethoxy-2-methylpropanoate (1.6 g, 10.95 mmol) in MeOH (14 mL) was treated drop-wise with a solution of KOH (1.228 g, 21.89 mmol) in water (7 mL) and stirred at RT overnight. The mixture was treated with water, washed with Et2O (2×) and the aqueous layer was acidified to pH 2 with 2M HCl. The mixture was extracted with EtOAc (4×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 2-ethoxy-2-methylpropanoic acid (1.1 g, 76%) as a colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 12.42 (s, 1H), 3.34 (q, J=7.0 Hz, 2H), 1.28 (s, 6H), 1.06 (t, J=7.0 Hz, 3H). washed with Et2O (2×) The mixture was extracted with EtOAc (4×) the combined organics were dried over MgSO4 concentrated to dryness