Triethylamine → Benzyl (2S,4R)-4-methoxy-2-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylate

HRID 1007641Notes

Reaction equation

HRID 1007641 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][C@@H:8]1[CH2:12][C@@H:11]([O:13][CH3:14])[CH2:10][N:9]1[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C(N(CC)CC)C>ClCCl>[CH3:14][O:13][C@H:11]1[CH2:10][N:9]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C@H:8]([CH2:7][O:6][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:12]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59971156benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidine-1-carboxylate

Product 1

HCID 86624405Benzyl (2S,4R)-4-methoxy-2-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

Methanesulfonyl chloride (0.175 mL, 2.26 mmol, 1.2 equiv) was added to a solution of (2S,4R)-2-(hydroxymethyl)-4-methoxy-1-pyrrolidinecarboxylate (3-3, 0.500 g, 1.88 mmol, 1 equiv) and triethylamine (0.394 mL, 2.83 mmol, 1.50 equiv) in dichloromethane (30 mL) at 0° C. The resulting mixture was warmed to 23° C. and stirred for 1 h. The reaction mixture was partitioned between saturated sodium bicarbonate solution and dichloromethane (2×40 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexane initially, grading to 100% EtOAc) to provide benzyl (2S,4R)-4-methoxy-2-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylate (3-4) as a light yellow oil. 1H NMR (300 MHz, CDCl3) major rotamer: δ 7.37-7.25 (br m, 5H), 5.17 (d, 1H, J=11.8 Hz), 5.10 (d, 1H, J=11.8 Hz), 4.65 (dd, 1H, J=8.3, 3.8 Hz), 4.24 (br m, 2H), 3.95 (m, 1H), 3.68 (br d, 1H, J=12.0 Hz), 3.45 (dd, 1H, J=12.0, 4.4 Hz), 3.30 (s, 3H), 2.88 (s, 3H), 2.39 (m, 1H), 2.12 (m, 1H).

Workup

  1. customThe reaction mixture was partitioned between saturated sodium bicarbonate solution and dichloromethane (2×40 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (100% hexane initially

Sources & evidence

ORD record
ord-8d4a60f4e133417b9da12eaf72aa0f11
Source dataset
uspto-grants-2004_09
Patent number
US06794393B1

Reaction notes

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