Isopropyl chloroformate → HCID 24882982, compound

HRID 2421079Notes

Reaction equation

HRID 2421079 reaction equation
Cl.Cl.[N:3]1([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH2:8][CH2:7][CH:6]([N:9]2[C@H:13]3[CH2:14][CH2:15][CH2:16][CH2:17][C@@H:12]3[NH:11][C:10]2=[O:18])[CH2:5][CH2:4]1.C(N(CC)CC)C.Cl[C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34].[OH-].[Na+]>ClCCl>[O:18]=[C:10]1[N:9]([CH:6]2[CH2:5][CH2:4][N:3]([CH:19]3[CH2:24][CH2:23][N:22]([C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])[CH2:21][CH2:20]3)[CH2:8][CH2:7]2)[C@H:13]2[CH2:14][CH2:15][CH2:16][CH2:17][C@@H:12]2[NH:11]1

Participants

6

Reactant 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 67215093HCID 67215093, compound

Product 1

HCID 24882982HCID 24882982, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(3aS,7aS)-1-(1,4′-bipiperidin-4-yl)hexahydro-1H-benzo[d]imidazol-2(3H)-one dihydrochloride (0.68 g, 1.79 mmol) was dissolved in dichloromethane (20 mL) and triethylamine (0.75 mL, 5.38 mmol) was added. Isopropyl chloroformate (1.792 mL, 1.79 mmol) (solution 1M in toluene) was added drop wise at 0° C. The mixture was stirred for 2 hours then diluted in dichloromethane (60 mL) and the mixture made basic with 1N NaOH. The phases were separated and aq. phase was extracted with dichloromethane (2×25 mL). The combined organic phases were washed with brine (5 mL) and concentrated under reduced pressure. The crude was then purified by high pH prep LCMS to provide the title compound as a white solid (560 mg, 80%). 1H NMR (400 MHz, CHLOROFORM-D): δ ppm 1.22 (d, J=6.25 Hz, 6H), 1.26-1.49 (m, 6H), 1.58-1.70 (m, 2H), 1.72-1.84 (m, 7H), 1.94 (d, J=11.33 Hz, 1H), 2.14-2.32 (m, 3H), 2.33-2.47 (m, 1H), 2.69 (t, J=13.09 Hz, 2H), 2.84-2.96 (m, 2H), 2.96-3.06 (m, 1H), 3.65-3.81 (m, 1H), 4.07-4.28 (m, 2H), 4.43 (s, 1H), 4.80-4.94 (m, 1H). MS (M+1): 393.2

Workup

  1. customThe phases were separated
  2. extractionaq. phase was extracted with dichloromethane (2×25 mL)
  3. washThe combined organic phases were washed with brine (5 mL)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was then purified by high pH

Sources & evidence

ORD record
ord-1eded1cf60c8460d86d3c8e21e4f91cd
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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