Tetrahydrofuran → HCID 59201519, compound

HRID 451803Notes

Reaction equation

HRID 451803 reaction equation
[CH:1]12[N:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:6]1[CH2:5][CH2:4][N:3]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:2]2.[CH:25]1([CH2:29][Mg]Br)[CH2:28][CH2:27][CH2:26]1.C1COCC1.[NH4+].[Cl-]>[Cu]I>[C:11]([O:10][C:8]([NH:7][C@H:1]1[C@H:6]([CH2:29][CH:25]2[CH2:28][CH2:27][CH2:26]2)[CH2:5][CH2:4][N:3]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:2]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 441270183-Benzyl 7-(tert-butyl) 3,7-diazabicyclo[4.1.0]heptane-3,7-dicarboxylateHCID 178419658HCID 178419658, compound

Product 1

HCID 59201519HCID 59201519, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

(±)-3-benzyl 7-tert-butyl 3,7-diaza-bicyclo[4.1.0]heptane-3,7-dicarboxylate (62 mg, 0.187 mmol), CuI (8 mg, 0.2 equiv), and a stirring bar were put in a 100-mL flask. The flask was evacuated and backfilled with N2 gas (3×). Dry THF (5 mL) was added and the mixture was cooled to −40° C. (Cyclobutylmethyl)magnesium bromide in THF (620 μL, 3 equiv., ˜0.89 M) was added slowly. After 8 min, the reaction mixture was allowed to warm slowly to rt. After 20 min, the reaction mixture turned black. After stirring a further 2 h the reaction was complete. Satd aq NH4Cl solution (5 mL) was added to quench the reaction. The reaction mixture was partitioned between EtOAc (50 mL) and satd aq NH4Cl solution (20 mL). The aqueous layer was extracted with EtOAc (20 mL). The combined EtOAc layers were washed with water (15 mL), brine (15 mL), and dried over Na2SO4. After concentration, the residue was purified by Gilson to afford (±)-trans-benzyl 3-(tert-butoxycarbonylamino)-4-(cyclobutylmethyl)piperidine-1-carboxylate (14 mg, 19% yield). MS ESI +ve m/z 425 (M+Na).

Workup

  1. customThe flask was evacuated
  2. additionDry THF (5 mL) was added
  3. additionwas added slowly
  4. waitAfter 20 min
  5. customto quench
  6. customthe reaction
  7. customThe reaction mixture was partitioned between EtOAc (50 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  9. washThe combined EtOAc layers were washed with water (15 mL), brine (15 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationAfter concentration
  12. customthe residue was purified by Gilson

Sources & evidence

ORD record
ord-253b0c9fac894f17b17a532e2ffa9bca
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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