Lithium Hydroxide → (S)-3-(3-methyl-3H-1,2,3-triazol-4-yl)-3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)propanoic acid

HRID 731194Notes

Reaction equation

HRID 731194 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]2[N:16]([CH3:20])[N:17]=[N:18][CH:19]=2)[CH2:9][C:10]([O:12]CC)=[O:11])=[CH:4][CH:3]=1.Br[CH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]2([CH3:36])[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+].[Li+].[OH-]>CN(C=O)C.O>[CH3:20][N:16]1[C:15]([C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]([CH3:36])([CH3:35])[C:25]=4[CH:24]=3)=[CH:7][CH:6]=2)[CH2:9][C:10]([OH:12])=[O:11])=[CH:19][N:18]=[N:17]1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 27355976-(Bromomethyl)-1,1,4,4-Tetramethyl-1,2,3,4-TetrahydronaphthaleneHCID 57835869(S)-ethyl 3-(4-hydroxyphenyl)-3-(3-methyl-3H-1,2,3-triazol-4-yl)propanoate

Product 1

HCID 24967392(S)-3-(3-methyl-3H-1,2,3-triazol-4-yl)-3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)propanoic acidYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 73.6 (0.15 mmol), 6-(bromomethyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene (0.18 mmol) and cesium carbonate (0.2 mmol) in DMF (2 mL), was stirred at room temperature for 16 hours. To the reaction mixture was added LiOH in water (1 mL, 1N solution), and the resulting mixture was stirred at 50° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 73 (26 mg, 0.06 mmol) after lyophilization. MS ESI (pos.) m/e 448.3 (M+H). 1H NMR (500 MHz) (CDCl3) δ 7.95 (1H, s), 7.71 (1H, s), 7.33-7.36 (2H, m), 7.20 (1H, dd, J=7.9, 1.5 Hz), 7.07 (2H, d, J=8.5 Hz), 6.97 (2H, d, J=8.9 Hz), 4.98 (2H, s), 4.51-4.55 (1H, m), 3.86 (3H, s), 3.11-3.17 (1 H, m), 3.01-3.07 (1H, m), 1.72 (4H, s), 1.31 (6H, s) 1.30 (6H, s).

Workup

  1. stirringthe resulting mixture was stirred at 50° C. for 3 hours
  2. filtrationThe mixture was filtered
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-50b496f3c45243e597e68300615c8190
Source dataset
uspto-grants-2009_09
Patent number
US07582803B2

Reaction notes

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