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

HRID 1455595Notes

Reaction equation

HRID 1455595 reaction equation
[CH:1]1([C:4]2[N:8]=[C:7]([CH:9]([OH:33])[CH:10]([NH:13][C:14]([CH:16]([NH:24][C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])[CH2:17][C:18]([F:23])([F:22])[CH2:19][CH2:20][CH3:21])=[O:15])[CH2:11][CH3:12])[O:6][N:5]=2)[CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>ClCCl.C([O-])(O)=O.[Na+]>[CH:1]1([C:4]2[N:8]=[C:7]([C:9]([C@@H:10]([NH:13][C:14]([C@@H:16]([NH:24][C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])[CH2:17][C:18]([F:23])([F:22])[CH2:19][CH2:20][CH3:21])=[O:15])[CH2:11][CH3:12])=[O:33])[O:6][N:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 86760809Morpholine-4-carboxylic acid (1-{1-[(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-hexyl)-amide

Product 1

HCID 11178915Morpholine-4-carboxylic acid {(s)-1-[(s)-1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-3,3-difluoro-hexyl}-amideYield 81.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of morpholine-4-carboxylic acid (1-{1-[(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-hexyl)-amide (145 mg, 0.31 mmol) in dry dichloromethane (3 mL) under N2 is added Dess-Martin periodinane (15% wt solution in dichloromethane, 1.73 g, 0.061 mmol). The reaction is stirred at room temperature for 2 hr, then quenched with a solution of Na2S2O3 193 mg, 1.22 mmol) in saturated NaHCO3 (30 mL). The aqueous layer is extracted with dichloromethane (2×30 mL). The organic layers are dried over magnesium sulfate and concentrated in vacuum. The residue is purified over 12 g silica gel, eluted with ethyl acetate: heptane (1:1 then 2:1) to afford the desired ketone (119 mg, 81%) as a solid.

Workup

  1. extractionThe aqueous layer is extracted with dichloromethane (2×30 mL)
  2. dry with materialThe organic layers are dried over magnesium sulfate
  3. concentrationconcentrated in vacuum
  4. customThe residue is purified over 12 g silica gel
  5. washeluted with ethyl acetate: heptane (1:1

Sources & evidence

ORD record
ord-b7e49a47dd6d4330a0912887488764a3
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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