Diethyl Ether → (3S,4R)-1-tert-butyl 3-ethyl 4-((R)-1-phenylethylamino)-piperidine-1,3-dicarboxylate

HRID 1593466Notes

Reaction equation

HRID 1593466 reaction equation
CCOCC.[C:6]1([C@H:12]([NH:14][C:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C:16]=2[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(#N)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(O)(=O)C>[C:6]1([C@H:12]([NH:14][C@@H:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[CH2:17][C@@H:16]2[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6342AcetonitrileHCID 5049666Sodium triacetoxyborohydrideHCID 10872460(R)-1-tert-butyl 3-ethyl 4-(1-phenylethylamino)-5,6-dihydropyridine-1,3(2H)-dicarboxylate

Product 1

HCID 66952586(3S,4R)-1-tert-butyl 3-ethyl 4-((R)-1-phenylethylamino)-piperidine-1,3-dicarboxylateYield 41%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

A 1L 3-neck round bottom flask equipped with a mechanical stirrer and addition funnel was charged with 252B (14.7 g, 39 mmol) and acetonitrile (200 mL) and acetic acid (100 mL). The solution was cooled to 0° C. and Na(OAc)3BH (33.3 g, 157 mmol) was added in three portions over 2 hours. The reaction was stirred for two hours at this temperature after the final addition. The mixture was then cooled to −10° C. and slowly quenched by addition of 1 N NaOH (100 mL), 4 N NaOH (100 mL), 6 N NaOH (100 mL) followed by 50% NaOH (50 mL). The reaction was warmed to room temperature and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×250 mL) and the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography (10% to 30% EtOAc/hexane gradient) on silica gel afforded 6.0 g (yield: 41%) of Compound 252C.

Workup

  1. additionaddition
  2. temperatureThe mixture was then cooled to −10° C.
  3. customslowly quenched by addition of 1 N NaOH (100 mL), 4 N NaOH (100 mL), 6 N NaOH (100 mL)
  4. temperatureThe reaction was warmed to room temperature
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with CH2Cl2 (2×250 mL)
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography (10% to 30% EtOAc/hexane gradient) on silica gel

Sources & evidence

ORD record
ord-9c99c915f4d9400cbfea7dae50405705
Source dataset
uspto-grants-2007_11
Patent number
US07297695B2

Reaction notes

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