Triacetoxyperiodinane → Perhydro-1,4-oxazepine-4-carboxylic acid {(S)-1-[(S)-1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-3,3-difluoro-butyl}-amide

HRID 1455606Notes

Reaction equation

HRID 1455606 reaction equation
[CH:1]1([C:4]2[N:8]=[C:7]([CH:9]([OH:32])[C@@H:10]([NH:13][C:14]([C@@H:16]([NH:22][C:23]([N:25]3[CH2:31][CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])[CH2:17][C:18]([F:21])([F:20])[CH3:19])=[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>ClCCl>[CH:1]1([C:4]2[N:8]=[C:7]([C:9]([C@@H:10]([NH:13][C:14]([C@@H:16]([NH:22][C:23]([N:25]3[CH2:31][CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])[CH2:17][C:18]([F:21])([F:20])[CH3:19])=[O:15])[CH2:11][CH3:12])=[O:32])[O:6][N:5]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 86607352Perhydro-1, 4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide

Product 1

HCID 11442479Perhydro-1,4-oxazepine-4-carboxylic acid {(S)-1-[(S)-1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-3,3-difluoro-butyl}-amideYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Perhydro-1,4-oxazepine-4-carboxylic acid ((S)-1-{(S)-1-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-hydroxy-methyl]-propylcarbamoyl}-3,3-difluoro-butyl)-amide (110 mg, 0.24 mmol) in dry dichloromethane (20 mL) under N2 is added Dess-Martin periodinane (143 mg, 0.34 mmol). The reaction is stirred at RT for 2 hr, and then dichloromethane (20 mL) is added. The reaction is quenched with a solution of Na2S2O3 (0.26M, 2 mL) and washed with saturated NaHCO3 (20 mL). The aqueous layer is extracted with dichloromethane (2×30 mL). The organic layers are dried (Na2SO4) and concentrated in vacuum. The residue is purified over 12 g silica gel, eluted with ethyl acetate: heptane (gradient 50-100%) to afford Perhydro-1,4-oxazepine-4-carboxylic acid {(S)-1-[(S)-1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-3,3-difluoro-butyl}-amide (82 mg, 75%) as a solid.

Workup

  1. customThe reaction is quenched with a solution of Na2S2O3 (0.26M, 2 mL)
  2. washwashed with saturated NaHCO3 (20 mL)
  3. extractionThe aqueous layer is extracted with dichloromethane (2×30 mL)
  4. dry with materialThe organic layers are dried (Na2SO4)
  5. concentrationconcentrated in vacuum
  6. customThe residue is purified over 12 g silica gel
  7. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-0d0688a122a845a4b3850f61bb03ce46
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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