Dimethyl Sulfoxide → methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyl-oxy)cyclopentyl]heptanate

HRID 883734Notes

Reaction equation

HRID 883734 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:14][C@@H:15]1[C@H:19]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[C@@H:18]([CH2:30][OH:31])[C@H:17]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:16]1)(=[O:13])[CH3:12].C(N(CC)CC)C>ClCCl.O>[C:11]([O:14][C@@H:15]1[C@H:19]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[C@@H:18]([CH:30]=[O:31])[C@H:17]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH2:16]1)(=[O:13])[CH3:12]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22789843Methyl 7-{(1R,2S,3R,5S)-5-(acetyloxy)-2-(hydroxymethyl)-3-[(oxan-2-yl)oxy]cyclopentyl}heptanoate

Product 1

HCID 11729034methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyl-oxy)cyclopentyl]heptanateYield 92.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of oxalyl chloride (28.3 ml, 324 mmol) in dichloromethane (325 ml) was cooled in a dry ice-methanol bath. Dimethylsulfoxide (46.0 ml, 648 mmol) was added drop wise and the mixture was stirred for approximately 30 minutes. A solution of methyl 7-[(1R,2S,3R,5S)-5-acetoxy-2-hydroxymethyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (28) (65.00 g, 162.3 mmol) in dichloromethane (170 ml) was added thereto drop wise and the mixture was stirred for approximately 1.5 hours. Triethylamine (113 ml, 811 mmol) was added drop wise to the reaction and the reaction mixture was warmed to 0° C. Water (426 ml) was added to the reaction mixture and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with t-butyl methyl ether (266 ml). The organic layers were combined and sequentially washed with 1N-hydrochloric acid (390 ml), water (426 ml), saturated sodium bicarbonate water (426 ml) and saturated aqueous sodium chloride (426 ml). After drying with anhydrous magnesium sulfate (54 g), the solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 1950 g; ethyl acetate:hexane =3:7) to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (59.74 g, 149.9 mmol; yield: 92.4%) as yellow oil.

Workup

  1. stirringthe mixture was stirred for approximately 1.5 hours
  2. customwise to the reaction
  3. stirringthe mixture was stirred
  4. customseparated into two layers
  5. extractionThe aqueous layer was extracted twice with t-butyl methyl ether (266 ml)
  6. washsequentially washed with 1N-hydrochloric acid (390 ml), water (426 ml), saturated sodium bicarbonate water (426 ml) and saturated aqueous sodium chloride (426 ml)
  7. dry with materialAfter drying with anhydrous magnesium sulfate (54 g)
  8. concentrationthe solution was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 1950 g; ethyl acetate:hexane =3:7)

Sources & evidence

ORD record
ord-048bfa906ab44e99800645cd55cbbeed
Source dataset
uspto-grants-2012_08
Patent number
US08236969B2

Reaction notes

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