Isopropyl chloroformate → HCID 25221336, compound

HRID 1642491Notes

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][CH:37]([CH3:39])[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][CH:37]([CH3:39])[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

Conditions

Temperature: 0 °C

Procedure

To a solution of (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, 0.76 mmol) in dichloromethane (10 mL) at 0° C. was added diisopropylethyl amine (0.315 g, 2.44 mmol) followed by isopropyl chloroformate (0.112 g, 0.92 mmol) dropwise over 30 minutes and stirred at 0° C. for 2 hours. The reaction was quenched with 1N NaOH and aqueous phase extracted with dichloromethane. The combined organic phases were dried and concentrated in vacuo. The residue was then purified by using preparative LC/MS (high pH) to provide the title compound (127 mg, 41%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.86 (s, 3H), 1.06-1.18 (m, 1H), 1.20 (d, J=6.25 Hz, 6H), 1.27-1.42 (m, 3H), 1.44-1.90 (m, 12H), 1.98-2.26 (m, 2H), 2.77-2.99 (m, 2H), 3.20-3.39 (m, 2H), 3.40-3.72 (m, 5H), 4.16-4.36 (m, 1H), 4.72-4.92 (m, 1H). MS (M+1): 407.30.

Workup

customThe reaction was quenched with 1N NaOH and aqueous phase
extractionextracted with dichloromethane
customThe combined organic phases were dried
concentrationconcentrated in vacuo
customThe residue was then purified

Sources & evidence

ORD record: ord-1763579804614d239ca08d0f4ab69c42
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119661B2

Reaction notes

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