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Lithium diisopropylamide was prepared by the addition of 2.45M N-butyl lithium (16.5 mL) in hexanes to a solution diisopropylamine (5.80 mL, 41.4 mmmol) in tetrahydrofuran (40 mL) at 0° C. with stirring for 20 minutes. Then a solution of tetrahydropyran-4-carboxylic acid (2.5 g, 19.2 mmol) in tetrahydrofuran (10 mL) was added to the solution of lithium diisopropylamide over 15 minutes to form a slurry, followed by hexamethylphosphoramide (2 mL). The resulting solution was stirred for 25 minutes, then immediately warmed to room temperature after a stream of gaseous formaldehyde (prepared by heating 4 g of paraformaldehyde at 175-200° C. over 5-10 minutes) was passed through the solution. The slurry was carefully concentrated at ambient temperature, acidified to pH 3 with 8M hydrochloric acid, saturated with solid sodium chloride, and extracted with ethyl acetate (8×100 mL). The combined organic layers were dried over magnesium sulfate, concentrated in vacuo. Chromatography over silica gel (80 g), and eluting with 10% methanol/methylene chloride, yielded 4-(hydroxymethyl)tetrahydropyran-4-carboxylic acid as a white solid (1.80 g, 58%). mp 113.7-115° C.; IR (KBr) 3420 (br), 1724 cm-1, 1HNMR (DMSO-d6) δ 1.43 (ddd, J=13.5, 11.0, 4.4 Hz, 2H), 1.85 (dm, J=13.4 Hz, 2H), 3.37 (td, J=11.3, 3.0 Hz, 2H), 3.43 (s, 2H), 3.71 (dt, J=11.6, 3.9 Hz, 2H), 4.81 (br, s, 1H); 12.24 (s, 1H); 13CNMR (DMSO-d6) δ 30.42 (t), 46.38 (s), 64.35 (t), 68.15 (t), 69.02 (t), 176.08 (s); HRMS Calcd. for C7H12O4 : 160.0735. Found: 160.0731. Anal. Calcd. for C7H12O3 : C, 52.49; H, 7.55. Found: C, 52.50; H, 7.62.

1. customto form a slurry
2. stirringThe resulting solution was stirred for 25 minutes
3. concentrationThe slurry was carefully concentrated at ambient temperature
4. extractionextracted with ethyl acetate (8×100 mL)
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. washChromatography over silica gel (80 g), and eluting with 10% methanol/methylene chloride