Diisopropylethylamine → 7-Chloro-9-(1-hydroxyethyl)-6-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one

HRID 626824Notes

Reaction equation

HRID 626824 reaction equation
C(OC([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:20]([CH:21]([OH:23])[CH3:22])=[CH:19][C:18]([Cl:24])=[C:17]([CH3:25])[C:13]=1[C:14](O)=[O:15])=O)(C)(C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>Cl.O1CCOCC1.C(OCC)(=O)C.CN(C)C=O>[Cl:24][C:18]1[CH:19]=[C:20]([CH:21]([OH:23])[CH3:22])[C:12]2[O:11][CH2:10][CH2:9][NH:8][C:14](=[O:15])[C:13]=2[C:17]=1[CH3:25]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27960291-Hydroxybenzotriazole hydrateHCID 866975182-{2-[(tert-Butoxycarbonyl)amino]ethoxy}-5-chloro-3-(1-hydroxyethyl)-6-methylbenzoic acid

Product 1

HCID 866975197-Chloro-9-(1-hydroxyethyl)-6-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-oneYield 76%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-{2-[(tert-Butoxycarbonyl)amino]ethoxy}-5-chloro-3-(1-hydroxyethyl)-6-methylbenzoic acid (27 mg, 0.072 mmol) was stirred in 4.0 M hydrogen chloride in 1,4-dioxane (3 mL) and evaporated. 1-Hydroxybenzotriazole hydrate (13 mg, 0.087 mmol), N,N-diisopropylethylamine (63 μL, 0.36 mmol) and N,N-dimethylformamide (2.0 mL) were added and the mixture was stirred for ten minutes. Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (38 mg, 0.087 mmol) was added and the mixture was stirred at 30° C. overnight. The mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and evaporated to give the desired product (14 mg, 76%). LCMS calculated for C12H15ClNO3 (M+H)+: m/z=256.1; found: 256.0.

Workup

  1. customevaporated
  2. stirringthe mixture was stirred at 30° C. overnight
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-c6dc85c881dc41889e1f17f9a5d9dadb
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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