1,2-Dichloroethane → HCID 178525119, compound

HRID 1044385Notes

Reaction equation

HRID 1044385 reaction equation
O=[CH:2][CH2:3][C:4]1([C:20]([O:22]CC)=O)[CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]1.Cl.[NH2:26][C@H:27]1[CH2:32][CH2:31][C@H:30]([OH:33])[CH2:29][CH2:28]1.C(N(CC)CC)C.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[OH:33][C@H:30]1[CH2:31][CH2:32][C@H:27]([N:26]2[CH2:2][CH2:3][C@:4]3([CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)=[O:11])[CH2:5]3)[C:20]2=[O:22])[CH2:28][CH2:29]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 598689161-Benzyl 3-ethyl 3-(2-oxoethyl)piperidine-1,3-dicarboxylateHCID 178479278HCID 178479278, compound

Product 1

HCID 178525119HCID 178525119, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-benzyl 3-ethyl 3-(2-oxoethyl)piperidine-1,3-dicarboxylate (1.0 g, 0.0030 mol, prepared by using procedures analogous to those described for the synthesis of example 1, steps 1 and 2), trans-4-aminocyclohexanol hydrochloride (0.50 g, 0.0033 mol), and triethylamine (0.48 g, 0.0048 mol) in 1,2-dichloroethane (8 mL, 0.1 mol) was stirred at rt for 30 min. To the mixture was added sodium triacetoxyborohydride (1.6 g, 0.0075 mol) and the resulting mixture was stirred at rt for 1 h. The reaction mixture then was warmed to 80° C. with stirring for 16 h. After cooling to ambient temperature, the reaction mixture was diluted with dichloromethane and the solution was washed with 1N HCl, water, brine, and dried over MgSO4. After filtration, the filtrate was concentrated in-vacuo and the resulting residue was purified by flash column chromatography to afford 1.04 g of the desired product. Further purification by chiral HPLC was carried out (Chiralcel OD-H column (3.0×25 cm, 5 micron particle size, Chiral Technologies; Item number 14475) eluting with 15% ethanol/hexanes (isocratic, 26 mL/min.); Detection: 220 nm; retention time: 10.0 minute for peak 1, 12.5 minute for peak 2). The first peak to elute was found to be the R configuration and the second peak was found to be the S configuration and used for analog synthesis. LC-MS: 387.3 (M+H)+.

Workup

  1. customprepared
  2. stirringthe resulting mixture was stirred at rt for 1 h
  3. temperatureThe reaction mixture then was warmed to 80° C.
  4. stirringwith stirring for 16 h
  5. temperatureAfter cooling to ambient temperature
  6. washthe solution was washed with 1N HCl, water, brine
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated in-vacuo
  10. customthe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-6b93cf6bbcc1454d8e46850aed7eb722
Source dataset
uspto-grants-2013_10
Patent number
US08563570B2

Reaction notes

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