Phenol → (R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate

HRID 2277051Notes

Reaction equation

HRID 2277051 reaction equation
C1(O)C=CC=CC=1.[OH:8][C@@H:9]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=1)[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH2:44][CH:45]2[CH2:50][CH2:49][N:48]([C:51](=[O:53])[CH3:52])[CH2:47][CH2:46]2)(=O)=O)=CC=1>CN(C=O)C.CCOC(C)=O>[C:51]([N:48]1[CH2:49][CH2:50][CH:45]([CH2:44][O:26][C:22]2[CH:21]=[C:20]([C@H:9]([OH:8])[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:25]=[CH:24][CH:23]=2)[CH2:46][CH2:47]1)(=[O:53])[CH3:52]

Participants

7

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 66569167(1-Acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate

Product 1

HCID 131733438(R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Phenol (7, Intermediate I) (0.850 g, 3.20 mmol) and K2CO3 (1.32 g, 9.60 mmol) were added to a solution of (1-acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonate (1.0 g, 3.20 mmol) in DMF (10 mL). The reaction mixture was heated at 90° C. overnight. The reaction mixture was diluted with EtOAc and washed with water and brine. Organic layer was dried over anhydrous Na2SO4) and concentrated under reduced pressure to give after purification by column chromatography to give (R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate as a colorless semi solid. Yield (600 mg, 46%); 1H NMR (400 MHz, DMSO-d6); δ 7.18 (d, J=4.0 Hz, 1H), 6.93 (s, 1H), 6.86 (d, J=7.6 Hz, 1H), 6.76 (d, J=6.0 Hz, 1H), 5.17 (d, J=4.4 Hz, 1H), 4.50 (d, J=4.8 Hz, 1H), 4.39 (d, J=11.6 Hz, 1H), 3.81 (d, J=6.4 Hz, 2H), 3.06-2.94 (m, 4H), 1.99 (s, 3H), 1.78 (t, J=14 Hz, 2H), 1.65 (t, J=7.2, 2H), 1.36 (s, 9H), 1.23 (s, 3H), 1.55-0.88 (m, 1H); MS: m/z 407.05 [M+H]+.

Workup

  1. washwashed with water and brine
  2. dry with materialOrganic layer was dried over anhydrous Na2SO4) and
  3. concentrationconcentrated under reduced pressure
  4. customto give
  5. customafter purification by column chromatography

Sources & evidence

ORD record
ord-c682c92df6a94351acaf235bd83eaeb9
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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