Acetyl chloride → HCID 68312735, compound

HRID 1530383Notes

Reaction equation

HRID 1530383 reaction equation
C(Cl)(=O)C.C(OC([N:12]1[CH2:17][CH2:16][CH2:15][CH:14]([O:18][C:19]2[CH:38]=[CH:37][C:22]3[C:23]4[N:27]([CH2:28][CH2:29][O:30][C:21]=3[CH:20]=2)[CH:26]=[C:25]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[N:24]=4)[CH2:13]1)=O)(C)(C)C>CO>[NH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([O:18][C:19]2[CH:38]=[CH:37][C:22]3[C:23]4[N:27]([CH2:28][CH2:29][O:30][C:21]=3[CH:20]=2)[CH:26]=[C:25]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[N:24]=4)[CH2:13]1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 68312825HCID 68312825, compound

Product 1

HCID 68312735HCID 68312735, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To an ice-cooled solution of MeOH (4 mL) was added dropwise acetyl chloride (1.5 mL) and the mixture was stirred for 30 min at RT. A solution of impure 3-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy)piperidine-1-carboxylic acid tertbutyl ester coming from the previous step in MeOH (1 mL) was then added and the reaction mixture was stirred for 2 h at RT. A white solid was filtered off and the filtrate was concentrated in vacuo. The resulting residue was purified by HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 35-85% 0.1% NH4OH in acetonitrile/water, RT 10.6 min) affording 8-(Piperidin-3-yloxy)-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (13 mg, 6% over two steps).

Workup

  1. stirringthe reaction mixture was stirred for 2 h at RT
  2. filtrationA white solid was filtered off
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe resulting residue was purified by HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 35-85% 0.1% NH4OH in acetonitrile/water, RT 10.6 min)

Sources & evidence

ORD record
ord-101c2d3926534d15b9ad79d16ec01fc0
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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