Ethyl chloroformate → HCID 25221335, compound

HRID 1642490Notes

Reaction equation

HRID 1642490 reaction equation
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(N(C(C)C)CC)(C)C.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35]>ClCCl>[O:23]=[C:15]1[N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:2]3([CH3:1])[CH2:7][CH2:6][N:5]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:4][CH2:3]3)[CH2:9][CH2:10]2)[C@H:18]2[CH2:19][CH2:20][CH2:21][CH2:22][C@H:17]2[NH:16]1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 57619831HCID 57619831, compound

Product 1

HCID 25221335HCID 25221335, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of crude (cis)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (HCl salt, 0.3 g) in dichloromethane (10 mL) was added diisopropylethyl amine (0.337 g, 2.61 mmol) followed by a solution of ethyl chloroformate (0.119 g, 1.09 mmol) in dichloromethane (1 mL) dropwise over 30 minutes at 0° C. and the mixture stirred at this temperature for 2 h. The mixture was then quenched by ice and diluted with dichloromethane and aqueous phase was extracted with dichloromethane. The combined organic phases were dried and concentrated in vacuo. The residue was then purified by preparative LC/MS (high pH) to provide the title compound as an off white solid (60 mg, 18%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.88 (s, 3H), 1.07-1.21 (m, 1H), 1.23 (t, J=7.03 Hz, 3H), 1.29-1.43 (m, 3H), 1.45-1.92 (m, 13H), 2.02-2.24 (m, 2H), 2.81-3.01 (m, 2H), 3.23-3.40 (m, 2H), 3.41-3.69 (m, 5H), 4.10 (q, J=7.29 Hz, 2H).

Workup

  1. customThe mixture was then quenched by ice
  2. additiondiluted with dichloromethane and aqueous phase
  3. extractionwas extracted with dichloromethane
  4. customThe combined organic phases were dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was then purified by preparative LC/MS (high pH)

Sources & evidence

ORD record
ord-faac403d8446492b89ff1621c72c3ecf
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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