Methyl chloroformate → HCID 118075673, compound

HRID 1051737Notes

Reaction equation

HRID 1051737 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[CH3:6][C@H:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:13]=2[O:17][CH2:18][CH2:19][CH3:20])[N:8]1[C:27](=[O:29])[CH3:28].C(N(CC)CC)C>ClCCl>[C:27]([N:8]1[C:9]2[C:14](=[C:13]([O:17][CH2:18][CH2:19][CH3:20])[C:12]([CH:21]3[CH2:26][CH2:25][N:24]([C:2]([O:4][CH3:5])=[O:3])[CH2:23][CH2:22]3)=[CH:11][CH:10]=2)[CH2:15][CH2:16][C@@H:7]1[CH3:6])(=[O:29])[CH3:28]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 118076148HCID 118076148, compound

Product 1

HCID 118075673HCID 118075673, compoundYield 97.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl chloroformate (5 μL, 0.06 mmol) was added to a solution of (S)-1-(2-methyl-6-(piperidin-4-yl)-5-propoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone (20 mg, 0.05 mmol) and triethylamine (0.04 mL, 0.27 mmol) in dichloromethane (0.5 mL), and the reaction stirred at room temperature overnight. The reaction was quenched via the addition of water (5 mL). The organic layer was collected and further washed with water (5 mL) and brine (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified via column chromatography on silica gel (Biotage 10 g column, gradient elution with 10-20% methanol in ethyl acetate) to afford methyl (S)-4-(1-acetyl-2-methyl-5-propoxy-1,2,3,4-tetrahydroquinolin-6-yl)piperidine-1-carboxylate (19 mg, 89%) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.94-1.07 (m, 6H), 1.17-1.26 (m, 1H), 1.43-1.57 (m, 2H), 1.60-1.79 (m, 4H), 2.01 (s, 3H), 2.16-2.31 (m, 2H), 2.68-2.91 (m, 3H), 2.95-3.03 (m, 1H), 3.58 (s, 3H), 3.61-3.73 (m, 2H), 4.04-4.15 (m, 2H), 4.56 (br d, J=6.45 Hz, 1H), 7.05 (br s, 2H). MS (ESI, pos. ion) m/z 389 [M+H]+.

Workup

  1. customThe reaction was quenched via the addition of water (5 mL)
  2. customThe organic layer was collected
  3. washfurther washed with water (5 mL) and brine (5 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via column chromatography on silica gel (Biotage 10 g column, gradient elution with 10-20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-a2ff43d3be41460fb36a2e405985e40c
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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