Phenol → (R)-tert-butyl (3-hydroxy-3-(3-(pyridin-4-ylmethoxy)phenyl)propyl)carbamate

HRID 2277045Notes

Reaction equation

HRID 2277045 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+].C1(O)C=CC=CC=1.[OH:22][C@@H:23]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([OH:40])[CH:35]=1)[CH2:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30]>CC(C)=O.CCOC(C)=O.O>[OH:22][C@@H:23]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH2:2][C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)[CH:35]=1)[CH2:24][CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30]

Participants

8

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 6427994-(Bromomethyl)pyridineHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate

Product 1

HCID 90444193(R)-tert-butyl (3-hydroxy-3-(3-(pyridin-4-ylmethoxy)phenyl)propyl)carbamate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(Bromomethyl)pyridine (298 mg, 1.17 mmol) and K2CO3 (774 mg, 5.61 mmol) were added to a solution of phenol (7, Intermediate I) (300 mg, 1.12 mmol) in acetone (20 mL). The reaction mixture was stirred overnight at ambient temperature, diluted with EtOAc and water. The organic layer was washed with 5% aq. NaOH, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (50% EtOAc:hexane) gave (R)-tert-butyl (3-hydroxy-3-(3-(pyridin-4-ylmethoxy)phenyl)propyl)carbamate (15) as dark brown solid. Yield (0.183 g, 46%); 1H NMR (400 MHz, DMSO-d6): δ 8.61 (d, J=5.2 Hz, 2H), 7.36 (d, J=5.2 Hz, 2H), 7.28-7.24 (m, 1H), 7.03 (s, 1H), 6.96 (d, J=8.0 Hz, 1H), 6.85-6.83 (m, 1H), 5.10 (s, 2H), 4.86 (bs, 1H), 4.74-4.71 (m, 1H), 3.52-3.49 (m, 1H), 3.39 (bs, 1H), 3.19-3.12 (m, 1H), 1.86-1.77 (m, 2H), 1.45 (s, 9H); MS: m/z 359.19 [M+H]+.

Workup

  1. washThe organic layer was washed with 5% aq. NaOH
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography (50% EtOAc:hexane)

Sources & evidence

ORD record
ord-5f61ca2ffa284be2ae3d72df76ceea38
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

Loading…