Trifluoroacetic acid → 8-nitro-3,4-dihydro-2H-1,4-benzoxazepin-5-one

HRID 1040927Notes

Reaction equation

HRID 1040927 reaction equation
C(OC([CH:8]([NH2:23])[CH2:9][O:10][C:11]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:12]=1[C:13](O)=[O:14])=O)(C)(C)C.C(O)(C(F)(F)F)=O.CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.CN([PH+](N(C)C)N(C)C)C>C(Cl)Cl.CN(C=O)C>[N+:20]([C:18]1[CH:17]=[CH:16][C:12]2[C:13](=[O:14])[NH:23][CH2:8][CH2:9][O:10][C:11]=2[CH:19]=1)([O-:22])=[O:21]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 27960291-Hydroxybenzotriazole hydrateHCID 22494795Tris(dimethylamino)phosphonium hexafluorophosphateHCID 866338942-(2-Tert-butoxycarbonyl amino-ethoxy)-4-nitro-benzoic acid

Product 1

HCID 578537818-nitro-3,4-dihydro-2H-1,4-benzoxazepin-5-oneYield 27.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2-tert-butoxycarbonyl amino-ethoxy)-4-nitro-benzoic acid (0.18 g, 0.00055 mol) in DCM (5 mL) was added TFA (0.5 mL) and stirred 1 hr. and evaporated. The residue was treated with anhydrous DMF (1 mL), N-methyl morpholine (0.50 mL 0.0046 mL) and 1-hydroxybenzotriazole hydrate (0.12 g, 0.00088 mol) and stirred 10 min. Benzotriazole-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.39 g, 0.00088 mol) was added, stirred 15 hrs. and evaporated. The residue was purified by ISCO chromatography giving 8-nitro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one (0.032 g, 26%) as a white solid. MP: 208-9° C.; 1H-NMR (DMSO-d6) δ 8.66 (s, 1H), 7.99-8.01 (d, 1H), 7.92-4 (d, 1H), 7.79-80 (d, 1H), 4.39-41 (m, 2H), 3.36-9 (m, 2H); LC/MS (ESI+): 209 (M+H).

Workup

  1. customand evaporated
  2. stirringstirred 10 min
  3. stirringstirred 15 hrs
  4. customand evaporated
  5. customThe residue was purified by ISCO chromatography

Sources & evidence

ORD record
ord-9f796634edc548e99e5c2e75ed64399a
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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