tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate → Tert-butyl 4-(2-(benzyloxy)benzyl)-4-hydroxypiperidine-1-carboxylate

HRID 706971Notes

Reaction equation

HRID 706971 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[Mg]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:17]1[C:19]2([CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)[CH2:18]1>O1CCCC1.[Cu]I>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:18][C:19]1([OH:17])[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylateHCID 178419625HCID 178419625, compound

Product 1

HCID 67126821Tert-butyl 4-(2-(benzyloxy)benzyl)-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

(2-(Benzyloxy)phenyl)magnesium bromide (33.8 mL, 1M) was added to a solution of EXAMPLE 263A (6.0 g) and CuI (1.07 g) in tetrahydrofuran (220 mL) at 0° C. over 10 minutes. The reaction was quenched with pH 7 buffer (20 mL), extracted twice with ether, and the combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was chromatographed on silica gel using 2-20% ethyl acetate in hexanes to provide the title compound.

Workup

  1. customThe reaction was quenched with pH 7 buffer (20 mL)
  2. extractionextracted twice with ether
  3. washthe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was chromatographed on silica gel using 2-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0ae8c2e77911497c9342eaf042fe7d46
Source dataset
uspto-grants-2015_11
Patent number
US09174982B2

Reaction notes

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