Ethylene Glycol → HCID 24871524, compound

HRID 2421876Notes

Reaction equation

HRID 2421876 reaction equation
C(N(CC)CC)C.ClC([O:11][CH2:12][CH3:13])=O.[OH:14][CH:15]([C:21]1[CH:26]=[CH:25][C:24]([N:27]2[C:31](=[O:32])[CH2:30][CH2:29][C@@H:28]2[CH2:33][CH2:34][CH2:35][C:36]2[S:40][C:39]([C:41]([OH:43])=[O:42])=[CH:38][CH:37]=2)=[CH:23][CH:22]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C(O)CO>>[OH:11][CH2:12][CH2:13][O:42][C:41]([C:39]1[S:40][C:36]([CH2:35][CH2:34][CH2:33][C@H:28]2[CH2:29][CH2:30][C:31](=[O:32])[N:27]2[C:24]2[CH:23]=[CH:22][C:21]([CH:15]([OH:14])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:26][CH:25]=2)=[CH:37][CH:38]=1)=[O:43]

Participants

5

Reactant 4

HCID 174Ethylene GlycolHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 11855868HCID 11855868, compound

Product 1

HCID 24871524HCID 24871524, compoundYield 43%

Procedure

Triethylamine (17.5 μL, 0.13 mmol) and ethyl chloroformate (6 μL, 0.063 mmol) were added sequentially to a solution 5-(3-{(S)-1-[4-(1-hydroxyhexyl)-phenyl]-5-oxo-pyrrolidin-2-yl}-propyl)-thiophene-2-carboxylic acid (derived from the faster eluting [HPLC] ester diastereomer, see U.S. Ser. No. 10/599,046 or U.S. Provisional Patent Application No. 60/777,506, filed on Feb. 28, 2006, incorporated by reference herein, 18 mg, 0.042 mmol) in CH2Cl2 (0.6 mL) at 0° C. The mixture was allowed to warm to room temperature. After 30 min at room temperature, ethylene glycol (25 μL, 0.45 mmol) was added. After stirring overnight at room temperature, the reaction mixture was concentrated under a stream of nitrogen. The residue was diluted with EtOAc (20 mL) and washed with H2O (2×5 mL) and brine (5 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→10% MeOH/CH2Cl2, gradient) afforded 8.5 mg (43%) of the title compound (1).

Workup

  1. washfaster eluting [HPLC] ester diastereomer
  2. customat 0° C
  3. concentrationthe reaction mixture was concentrated under a stream of nitrogen
  4. additionThe residue was diluted with EtOAc (20 mL)
  5. washwashed with H2O (2×5 mL) and brine (5 mL)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→10% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-0b5aff84753946299230ac48451bdebe
Source dataset
uspto-grants-2011_06
Patent number
US07960381B2

Reaction notes

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