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

HRID 2040238Notes

Reaction equation

HRID 2040238 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-a950faf52bf24ad3bb1f288f4764f07c
Source dataset
uspto-grants-2013_11
Patent number
US08580794B2

Reaction notes

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