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With thionyl chloride; In methanol; at 0 - 23℃; for 16.025h;
To a stirred solution [OF 4R-HYDROXYPYRROLIDINE-2R-CARBOXYLIC] acid (10.0 g, 76.3 mmol, [1] eq. ) in [MEOH] (300 mL) at [0 °C] was added SOC12 (10.0 mL, excess) over the course of 1.5 min. The reaction was allowed to warm to [23 °C.] After 16 h the reaction mixture was concentrated in vacuo to give 4R-hydroxypyrrolidine-2R-carboxylic acid methyl ester hydrochloride salt as a white solid (15.9 g, 100percent yield)
90%
With thionyl chloride; at 0 - 20℃; for 72h;
To a solution of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid 31.1 (1.0 eq) in MeOH (31 eq) at 0 °C was added S0C12 (1.2 eq) dropwise. The reaction solution was stirred at rt for 72 h. The resulting mixture was concentrated in vacuo to afford the compound 31.2 (90percent yield) as a white solid. LCMS (m/z): 146.0 [M+H] +. 1H NMR (400 MHz, DMSO-i/6) 3: 4.44 (d, J = 6.8 Hz, 1H), 4.33 (s, 1H), 3.70 (s, 3H), 3.03-3.00 (m, 1H), 2.30-2.23 (m, 1H), 2.14-2.09 (m, 1H), 1.17 (t, J = 7.2 Hz, 1H).
With acetyl chloride; for 8h;Inert atmosphere; Reflux;
[0346] Acetyl chloride (2.45 mL, 34.53mmoles) was slowly added to MeOH (25mL) in a reaction flask under inert atmosphere. To this was added a solution of Cis-4-Hydroxy-D- proline (3.235g, 24.67 mmol) and refluxed for 8h. The reaction mixture was cooled to room temperature, and poured into ether (200mL). The precipitated solid was suction filtered and dried to yield (2R,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride in quantitative yield. This was taken forward without purification.
With thionyl chloride; In methanol; at 10 - 65℃; for 2h;
To a suspension of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (100 g, 0.763 mol) in MeOH (1 L) was added SOd2 (115 g, 0.966 mcI) slowly at 10 C. Then the reaction was heated at 65 C for 2 hrs. The mixture was concentrated under high vacuum. The residue was washed with ether, filtered to give the title compound 0350 (138 g, 100% yield) as a yellow solid.LCMS: 146 [M+H]. tR =0.366 mins. (LCMS condition 3)
113%
With thionyl chloride; In methanol;
Step A-1. Preparation of an ester compound To a suspension of cis-4-hydroxy-D-proline (16.46 g: 125.5 mmole) in methanol (66 ml), thionylchloride (9.16 ml: 125.5 mmole) is added in a nitrogen atmosphere under ice cooling, and the mixture is stirred at room temperature for 30 minutes. The mixture is further stirred to react at 40 C. for 4 hours to give (2R,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride as crude crystals (25.74 g). Yield: 113%. Colorless crystals. NMR delta(D2 O) ppm: 2.3 to 2.6(m, 2H), 3.33(s, 1H), 3.4 to 3.5(m, 2H), 3.84(s, 3H), 4.6 to 4.7(m, 2H). IR nu (KBr) cm-1: 3320, 2980, 1728.