Potassium trimethylsilanolate → HCID 24954826, compound

HRID 1801609Notes

Reaction equation

HRID 1801609 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([CH2:19][NH:20][C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH3:22])=[CH:15][C:3]=1[O:4][CH2:5][C:6]1[O:7][CH:8]=[C:9]([C:11]([O:13]C)=[O:12])[N:10]=1.C[Si](C)(C)[O-].[K+]>C1COCC1>[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([CH2:19][NH:20][C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH3:22])=[CH:15][C:3]=1[O:4][CH2:5][C:6]1[O:7][CH:8]=[C:9]([C:11]([OH:13])=[O:12])[N:10]=1

Participants

4

Reactant 2

HCID 23668039Potassium trimethylsilanolateHCID 24954458HCID 24954458, compound

Product 1

HCID 24954826HCID 24954826, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-methyl 2-((2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenoxy)methyl)oxazole-4-carboxylate 102 (69 mg, 159 μmol) in 2 mL of dry THF, was added potassium trimethylsilanolate (22 mg, 174 μmol). The solution was stirred at ambient temperature for 2 h. The reaction was concentrated and the resulting crude material was purified with reverse phase preparatory HPLC. The desired fractions were combined and lyophilized to give (R)-2-((2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenoxy)methyl)oxazole-4-carboxylic acid 103 (41 mg, 61% yield) as a white solid and as the TFA salt. 1H NMR (400 MHz, d4-methanol) δ ppm 1.68-1.74 (m, 3H) 4.02 (d, J=13.30 Hz, 1H) 4.20 (d, J=13.30 Hz, 1H) 4.48 (q, J=6.85 Hz, 1H) 5.34 (s, 2H) 7.04 (dd, J=8.22, 1.76 Hz, 1H) 7.33 (d, J=1.76 Hz, 1H) 7.43-7.52 (m, 4H) 7.56 (s, 1H) 8.60 (s, 1H). Mass spectrum: calculated for C20H18Cl2N2O4 421.3. found 422.4 (M++1).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe resulting crude material was purified with reverse phase preparatory HPLC

Sources & evidence

ORD record
ord-09187d0448f84b14bb0ccdf6f4e5a607
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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