Methyl 2-bromobenzoate → Tert-butyl 4-hydroxy-4-phenylpiperidine-1-carboxylate

HRID 2276320Notes

Reaction equation

HRID 2276320 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=O.CC1(C)C(C)(C)OB(C2[CH2:21][CH2:22][NH:23][CH2:24][CH:25]=2)O1.[C:27]([O-:30])(O)=[O:28].[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:3]([O:30][C:27]([N:23]1[CH2:22][CH2:21][C:4]([OH:6])([C:3]2[CH:2]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:25][CH2:24]1)=[O:28])([CH3:8])([CH3:4])[CH3:2]

Participants

7

Reactant 3

HCID 11894Methyl 2-bromobenzoateHCID 516892Sodium BicarbonateHCID 211054611,2,3,6-Tetrahydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 11231242Tert-butyl 4-hydroxy-4-phenylpiperidine-1-carboxylateYield 98%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 2-bromobenzoate (1.816 ml, 12.936 mmol) [CAS 610-94-6] was added to a solution of 1,2,3,6-tetrahydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridine (4 g, 12.936 mmol) [CAS 375853-82-0] (synthesis described in WO 2004072025 A2 20040826) in 1,4-dioxane (28 ml) and an aqueous saturated solution of NaHCO3 (24 ml). The resulting solution was degassed using a stream of nitrogen and Pd(PPh3)4 (0.747 g, 0.647 mmol) was added to this solution. The reaction was then microwaved in a sealed tube at 140° C. for 5 minutes. The resulting cooled reaction mixture was then diluted with EtOAc and filtered through a pad of diatomaceous earth. The filtrate was collected, dried over Na2SO4 and concentrated in vacuo. The crude reaction mixture was then purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 6% as eluent). The desired fractions were collected and evaporated in vacuo to yield D21 (4.04 g, 98%).

Workup

  1. customThe resulting solution was degassed
  2. additionwas added to this solution
  3. customThe reaction was then microwaved in a sealed tube at 140° C. for 5 minutes
  4. temperatureThe resulting cooled
  5. customreaction mixture
  6. filtrationfiltered through a pad of diatomaceous earth
  7. customThe filtrate was collected
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude reaction mixture
  11. customwas then purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 6% as eluent)
  12. customThe desired fractions were collected
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-94129a29d7ab4841898c2885d5500dc2
Source dataset
uspto-grants-2015_09
Patent number
US09132122B2

Reaction notes

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