Hexahydro-1,4-diazepine → HCID 46855231, compound

HRID 882765Notes

Reaction equation

HRID 882765 reaction equation
[C:1]([N:4]1[CH2:9][C@H:8]2[CH2:10][C@@H:5]1[C:6](=[O:11])[O:7]2)(=[O:3])[CH3:2].[NH:12]1[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>C(O)(CC)(C)C>[N:12]1([C:6]([C@H:5]2[CH2:10][C@@H:8]([OH:7])[CH2:9][N:4]2[C:1](=[O:3])[CH3:2])=[O:11])[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 68163Hexahydro-1,4-diazepineHCID 11298087HCID 11298087, compound

Product 1

HCID 46855231HCID 46855231, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 64052-Methyl-2-butanolSolvent

Procedure

A mixture of (1R,4R)-5-acetyl-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one (310.3 g, 2.0 mol) and [1,4]diazepane (500.85 g, 5 mol) in t-amyl alcohol (3.0 L) was held at 90° C. for 17 h. The mixture was then concentrated to remove t-amyl alcohol (2.4 L). The resulting slurry was filtered and washed with EtOAc (1 L) to provide the title compound as a solid (367 g, 72%). MS (ESI): mass calcd. for C12H21N3O3, 255.2; m/z found, 256.2 [M+H]+. 1H NMR (CDCl3): 5.95 (br s, 1H), 4.93-4.68 (m, 1H), 4.48-4.32 (m, 1H), 3.90-3.65 (m, 5H), 3.54-3.41 (m, 1H), 3.12-2.74 (m, 4H), 2.32-2.22 (m, 1H), 2.16-1.68 (m, 6H).

Workup

  1. concentrationThe mixture was then concentrated
  2. customto remove t-amyl alcohol (2.4 L)
  3. filtrationThe resulting slurry was filtered
  4. washwashed with EtOAc (1 L)

Sources & evidence

ORD record
ord-c4bb471b57e0490f82e2b745623f3111
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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