Triacetoxyperiodinane → morpholine-4-carboxylic acid {(R)-2-cyclopropylmethanesulfonyl-1-[(S)-1-(5-trifluoromethyl-1,2,4-oxadiazole-3-carbonyl)-propylcarbamoyl]-ethyl}-amide

HRID 489642Notes

Reaction equation

HRID 489642 reaction equation
[CH:1]1([CH2:4][S:5]([CH2:8][C@H:9]([NH:27][C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[C:10](=[O:26])[NH:11][C@H:12]([CH:15]([OH:25])[C:16]2[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=2)[CH2:13][CH3:14])(=[O:7])=[O:6])[CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[CH:1]1([CH2:4][S:5]([CH2:8][C@H:9]([NH:27][C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[C:10](=[O:26])[NH:11][C@H:12]([C:15]([C:16]2[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=2)=[O:25])[CH2:13][CH3:14])(=[O:6])=[O:7])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 86590023morpholine-4-carboxylic acid ((R)-2-cyclopropylmethanesulfonyl-1-{(S)-1-[hydroxy-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide

Product 1

HCID 60054532morpholine-4-carboxylic acid {(R)-2-cyclopropylmethanesulfonyl-1-[(S)-1-(5-trifluoromethyl-1,2,4-oxadiazole-3-carbonyl)-propylcarbamoyl]-ethyl}-amideYield 2.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of morpholine-4-carboxylic acid ((R)-2-cyclopropylmethanesulfonyl-1-{(S)-1-[hydroxy-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide (370 mg, 0.70 mmol) in methylene chloride (10 mL) was treated with Dess Martin periodinane (298 mg, 0.70 mmol) and stirred at room temperature for 3 hours. The reaction mixture was washed with an aqueous solution of Na2S2O3 (0.26M), saturated aqueous bicarbonate solution and water, dried over Na2SO4 and the solvent evaporated under reduced pressure. The crude was subjected to flash chromatography eluting with a mixture of ethyl acetate and heptane. It was then further subjected to preparative HPLC (using Gilson 215 liquid handler, and MonoChrom 10 microns C18 column—PN0504—100×212 from MetaChem), eluting with a mixture of acetonitrile and water, going from 10% to 100% acetonitrile in water to give morpholine-4-carboxylic acid {(R)-2-cyclopropylmethanesulfonyl-1-[(S)-1-(5-trifluoromethyl-1,2,4-oxadiazole-3-carbonyl)-propylcarbamoyl]-ethyl}-amide as a white solid (9 mg). 1H NMR (CDCl3): 7.87 (d, J=6 Hz, 1H), 5.99 (d, J=6 Hz, 1H), 5.16 (m, 1H), 4.87 (m, 1H), 3.74-3.66 (m, 5H), 3.44-3.36 (m, 5H), 3.14 (d, J=7 Hz, 2H), 2.20-2.02 (m, 1H), 1.98-1.78 (m, 1H), 1.21 (m, 1H), 1.02 (t, J=7 Hz, 3H), 0.82-0.70 (m, 2H), 0.57-0.40 (m, 2H). MS: 526 (MH+)

Workup

  1. washThe reaction mixture was washed with an aqueous solution of Na2S2O3 (0.26M), saturated aqueous bicarbonate solution and water
  2. dry with materialdried over Na2SO4
  3. customthe solvent evaporated under reduced pressure
  4. washeluting with a mixture of ethyl acetate and heptane
  5. washeluting with a mixture of acetonitrile and water

Sources & evidence

ORD record
ord-420a2b30928849b7a4f22bb11a0ab76f
Source dataset
uspto-grants-2005_12
Patent number
US06977256B2

Reaction notes

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