tert-Butyl 4-oxopiperidine-1-carboxylate → 4-(4-Amino-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1262118Notes

Reaction equation

HRID 1262118 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[Si](C)(C)CC[Si]2(C)C)=[C:4]([O:17][CH3:18])[CH:3]=1.[Mg].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>C1COCC1>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][C:30]([C:2]2[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([O:17][CH3:18])[CH:3]=2)([OH:33])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5462224MagnesiumHCID 66710939HCID 66710939, compound

Product 1

HCID 667109494-(4-Amino-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(4-Bromo-2-methoxy-phenyl)-2,2,5,5-tetramethyl-[1,2,5]azadisilolidine (250 mg, 1.0 equiv) was dissolved in anhydrous THF (4 ml) under an argon atmosphere. A 1M suspension of magnesium in THF (0.941 ml, 1.33 equiv) was added dropwise at room temperature, and the mixture was stirred for 2 hours. It was then transferred via cannula to a room temperature solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (145 mg, 1.0 equiv), and the mixture was heated to reflux 2 hours. Cooled to room temperature and quenched with water. Partitioned between EtOAc/water. Dried over sodium sulfate and concentrated. Purified by preparative TLC, 40% EtOAc/hexane. Obtained 4-(4-amino-3-methoxy-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester as a purple foam, 52 mg. LCMS (E/I+) 323 (M+H). NMR 1H (CDCl3) 6.95 (s, 1H), 6.83 (d, J=5.82 Hz, 1H), 6.62 (d, J=5.73 Hz, 1H), 3.92-4.05 (m, 2H), 3.88 (s, 3H), 3.17-3.30 (m, 2H), 1.89-2.10 (m, 2H), 1.68-1.74 (m, 2H), 1.46 (s, 9H), 1.23 (s, 1H).

Workup

  1. customwas then transferred via cannula to a room temperature
  2. temperaturethe mixture was heated
  3. temperatureto reflux 2 hours
  4. customquenched with water
  5. customPartitioned between EtOAc/water
  6. dry with materialDried over sodium sulfate
  7. concentrationconcentrated
  8. customPurified by preparative TLC, 40% EtOAc/hexane

Sources & evidence

ORD record
ord-a7e7a74b182841bc986c40ee0ff89e0f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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