Sulfuric acid magnesium salt (1:1) → 4-(((2-(Tert-butoxy)-2-oxoethyl)amino)methyl)-3-methoxyphenyl 4-(heptyloxy)benzoate

HRID 923564Notes

Reaction equation

HRID 923564 reaction equation
[CH2:1]([O:8][C:9]1[CH:27]=[CH:26][C:12]([C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]=O)=[C:18]([O:24][CH3:25])[CH:17]=2)=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].Cl.[NH2:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>C(OCC)C.C1COCC1.CO>[CH2:1]([O:8][C:9]1[CH:27]=[CH:26][C:12]([C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][NH:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[C:18]([O:24][CH3:25])[CH:17]=2)=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 2725036Glycine tert-butyl ester hydrochlorideHCID 4311764Sodium borohydrideHCID 892531414-Formyl-3-methoxyphenyl 4-(heptyloxy)benzoate

Product 1

HCID 892531174-(((2-(Tert-butoxy)-2-oxoethyl)amino)methyl)-3-methoxyphenyl 4-(heptyloxy)benzoateYield 60.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Prepared using General Procedure 12: A suspension of 4-formyl-3-methoxyphenyl 4-(heptyloxy)benzoate (340 mg, 0.918 mmol) INT-25, tert-butyl 2-aminoacetate HCl (154 mg, 0.918 mmol), TEA (128 μL, 0.918 mmol) and magnesium sulfate (500 mg) in diethyl ether (20 mL) was stirred vigorously for 18 h. The reaction mixture was filtered and solvent removed under vacuum. Crude material was taken up into THF/MeOH (10 mL, 10 mL) and sodium borohydride (34.7 mg, 0.918 mmol) added with cooling to 0° C. After stirring for 1 h at room temperature the reaction was quenched with NaHCO3 (10 mL) and the solvent removed under vacuum. The residue was diluted with NaHCO3 (50 mL) and the product extracted with EA (100 mL). The organic extracts were combined and washed with brine (100 mL) and pre-absorbed onto silica gel then purified by chromatography (EA/isohexanes) to afford 270 mg (58%) of 4-(((2-(tert-butoxy)-2-oxoethyl)amino)methyl)-3-methoxyphenyl 4-(heptyloxy)benzoate INT-26 as a white solid. LCMS-ESI (m/z) calculated for C28H39NO6: 485; found 486 [M+H]+, tR=2.23 min (Method 10).

Workup

  1. customPrepared
  2. filtrationThe reaction mixture was filtered
  3. customsolvent removed under vacuum
  4. additionadded
  5. stirringAfter stirring for 1 h at room temperature the reaction
  6. customwas quenched with NaHCO3 (10 mL)
  7. customthe solvent removed under vacuum
  8. additionThe residue was diluted with NaHCO3 (50 mL)
  9. extractionthe product extracted with EA (100 mL)
  10. washwashed with brine (100 mL)
  11. custompre-absorbed onto silica gel
  12. customthen purified by chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-7c9244722a0e49bdbc2292a1ad66dfd7
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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