Triethylamine → HCID 24999337, compound

HRID 2421877Notes

Reaction equation

HRID 2421877 reaction equation
C(N(CC)CC)C.ClC(OCC)=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].O[CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1>>[N:47]1([CH2:46][CH2:45][O:42][C:41]([C:39]2[S:40][C:36]([CH2:35][CH2:34][CH2:33][C@H:28]3[CH2:29][CH2:30][C:31](=[O:32])[N:27]3[C:24]3[CH:23]=[CH:22][C:21]([CH:15]([OH:14])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:26][CH:25]=3)=[CH:37][CH:38]=2)=[O:43])[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 611632-MorpholinoethanolHCID 11855868HCID 11855868, compound

Product 1

HCID 24999337HCID 24999337, compoundYield 37%

Procedure

Triethylamine (17.5 μL, 0.13 mmol) and ethyl chloroformate (6 μL, 0.063 mmol) were added sequentially to a solution of 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. 60/777,506, 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, 4-(2-hydroxyethyl)morpholine (51 μL, 0.42 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 (37%) of the title compound (2).

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-b5a2e04ff92045d887a18bca95aa94f6
Source dataset
uspto-grants-2011_06
Patent number
US07960381B2

Reaction notes

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