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

HRID 723471Notes

Reaction equation

HRID 723471 reaction equation
[C:1]1([C@H:7]([NH:9][C:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:11]=2[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(#N)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(O)(=O)C>[C:1]1([C@H:7]([NH:9][C@@H:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:12][C@@H:11]2[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 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 CH2Cl22 (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 CH2Cl22 (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-06abaae98af144a4830b33234de064c5
Source dataset
uspto-grants-2006_11
Patent number
US07141571B2

Reaction notes

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