1-Hydroxybenzotriazole → tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-({[(1-methylethoxy)acetyl]amino}methyl)-1,4-oxazepane-4-carboxylate

HRID 1022630

Reaction equation

HRID 1022630 reaction equation
[NH2:1][CH2:2][C@H:3]1[C@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[CH:11]=2)[O:8][CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:4]1.[CH3:25][CH:26]([O:28][CH2:29][C:30](O)=[O:31])[CH3:27].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C1COCC1.C(N(CC)CC)C>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C@@H:9]2[O:8][CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:4][C@H:3]2[CH2:2][NH:1][C:30](=[O:31])[CH2:29][O:28][CH:26]([CH3:27])[CH3:25])=[CH:11][C:12]=1[F:17]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 5172132-(Propan-2-yloxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66975002tert-butyl (6R,7R)-6-(aminomethyl)-7-(4-chloro-3-fluorophenyl)-1,4-oxazepane-4-carboxylate

Product 1

HCID 66975815tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-({[(1-methylethoxy)acetyl]amino}methyl)-1,4-oxazepane-4-carboxylateYield 100.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of tert-butyl (6R,7R)-6-(aminomethyl)-7-(4-chloro-3-fluorophenyl)-1,4-oxazepane-4-carboxylate (300 mg), (1-methylethoxy)acetic acid (119 mg), 1H-benzotriazol-1-ol (136 mg) and triethylamine (0.291 ml) in THF (4.2 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (192 mg), and the mixture was stirred at room temperature overnight. To the reaction mixture was added distilled water, and the mixture was extracted with ethyl acetate. The extract was washed with distilled water and brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (384 mg).

Workup

  1. additionTo the reaction mixture was added
  2. distillationdistilled water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with distilled water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e983728b8b4e4c029f430f4452e2c52d
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Linked notes

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