Sodium Thiosulfate → morpholine-4-carboxylic acid {(S)-1-[(S)-1-(5-cyclopropyl-1,3,4-oxadiazole-2-carbonyl)-propylcarbamoyl]-3,3-difluoro-hexyl}-amide

HRID 1455597Notes

Reaction equation

HRID 1455597 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH:23]1([C:26]2[O:30][C:29]([CH:31]([OH:55])[C@@H:32]([NH:35][C:36]([C@@H:38]([NH:46][C:47]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:48])[CH2:39][C:40]([F:45])([F:44])[CH2:41][CH2:42][CH3:43])=[O:37])[CH2:33][CH3:34])=[N:28][N:27]=2)[CH2:25][CH2:24]1.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH:23]1([C:26]2[O:30][C:29]([C:31]([C@@H:32]([NH:35][C:36]([C@@H:38]([NH:46][C:47]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:48])[CH2:39][C:40]([F:45])([F:44])[CH2:41][CH2:42][CH3:43])=[O:37])[CH2:33][CH3:34])=[O:55])=[N:28][N:27]=2)[CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 86607347morpholine-4-carboxylic acid ((S)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl-}3,3-difluoro-hexyl)-amide

Product 1

HCID 11454227morpholine-4-carboxylic acid {(S)-1-[(S)-1-(5-cyclopropyl-1,3,4-oxadiazole-2-carbonyl)-propylcarbamoyl]-3,3-difluoro-hexyl}-amideYield 72.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Dess-Martin Periodinane (15 wt % in DCM, 0.79 gm, 0.28 mmol) is added to a solution of morpholine-4-carboxylic acid ((S)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-hexyl)-amide (67 mg, 0.14 mmol) in dry methylene chloride (10 mL) and stirred at room temperature for 2.5 hours. The reaction is quenched with a solution of Na2S2O3 (110.68 mg, 0.70 mmol) in aqueous NaHCO3. The organic layer is separated and the aqueous extracted with dichloromethane. The organic extracts are dried over sodium sulfate and concentrated under reduced pressure. Column chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate gives morpholine-4-carboxylic acid {(S)-1-[(S)-1-(5-cyclopropyl-1,3,4-oxadiazole-2-carbonyl)-propylcarbamoyl]-3,3-difluoro-hexyl}-amide as a powder (48 mg).

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous extracted with dichloromethane
  3. dry with materialThe organic extracts are dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionColumn chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-8abce0f9d9bc4fd3866008db7c670f23
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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