Dimethyl Sulfoxide → HCID 59924629, compound

HRID 1860508Notes

Reaction equation

HRID 1860508 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]1([C@@H:17]([N:28]2[CH2:32][C@H:31]([CH2:33][OH:34])[C@@H:30]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=3)[CH2:29]2)[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1>C(Cl)Cl>[CH:11]1([C@@H:17]([N:28]2[CH2:32][C@H:31]([CH:33]=[O:34])[C@@H:30]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=3)[CH2:29]2)[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 90789203HCID 90789203, compound

Product 1

HCID 59924629HCID 59924629, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

A solution of oxalyl chloride (1.03 mL, 11.8 mmol) in 60 mL CH2Cl2 was cooled in a dry ice/acetone bath. DMSO (1.67 mL, 23.6 mmol) was added dropwise. The mixture was stirred for 15 min then a solution of benzyl (2R)-cyclohexyl[(3S,4R)-3-(3-fluorophenyl)-4-(hydroxymethyl)pyrrolidin-1-yl]ethanoate (4.2 g, 9.8 mmol, from Step C) in 70 mL CH2Cl2 was added dropwise. After stirring for 15 min TEA (6.8 mL, 49 mmol) was added in 10 mL CH2Cl2. The mixture was warmed to rt and stirred for 2 h. The solution was poured into a speparatory funnel and diluted with 200 mL CH2Cl2 and washed with 1 N NaOH (2×), water and sat'd NaCl. The organic portion was dried over sodium sulfate and concentrated. Flash chromatography (150 g silica, 0→30% EtOAc/hexanes) gave the desired aldehyde. 1H NMR (500 MHz, CDCl3) δ0.95-1.05 (m, 2H), 1.14-1.29 (m, 3H), 1.6 (br d, 1H), 1.66-1.83 (m, 4H), 1.93 (br d, 1H), 2.65-2.69 (m, 1H), 2.88-2.93 m, 1H), 3.15 (dd, 1H), 3.20-3.24 (m, 2H), 3.27-3.30 (m, 1H), 3.55 (dd, 1H), 5.18 (d, 1H), 5.19 (d, 1H), 6.89-6.97 m, 3H), 7.23-7.27 (m, 1H), 7.33-7.4 (m, 5H).

Workup

  1. stirringstirred for 2 h
  2. additionThe solution was poured into a speparatory funnel
  3. washwashed with 1 N NaOH (2×), water
  4. dry with materialThe organic portion was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-270d96decbfc438e865bfb868bb5ddc2
Source dataset
uspto-grants-2003_03
Patent number
US06531484B2

Reaction notes

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