Triethylamine → (R)-methyl 2-(4-fluoro-3,5-dimethylphenylamino)-6-(4-fluoro-3-methylbenzylamino)hexanoate

HRID 885510Notes

Reaction equation

HRID 885510 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C@H:4]([NH:10][C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([F:18])=[C:13]([CH3:19])[CH:12]=1)[CH2:5][CH2:6][CH2:7][CH2:8][NH2:9].[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][C:23]=1[CH3:30].C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[F:18][C:14]1[C:15]([CH3:17])=[CH:16][C:11]([NH:10][C@H:4]([CH2:5][CH2:6][CH2:7][CH2:8][NH:9][CH2:26][C:25]2[CH:28]=[CH:29][C:22]([F:21])=[C:23]([CH3:30])[CH:24]=2)[C:3]([O:2][CH3:1])=[O:20])=[CH:12][C:13]=1[CH3:19]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27348744-Fluoro-3-methylbenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69169741(R)-6-Amino-2-(4-fluoro-3,5-dimethyl-phenylamino)-hexanoic acid methyl ester

Product 1

HCID 69170370(R)-methyl 2-(4-fluoro-3,5-dimethylphenylamino)-6-(4-fluoro-3-methylbenzylamino)hexanoateYield 87.5%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (R)-6-amino-2-(4-fluoro-3,5-dimethyl-phenylamino)-hexanoic acid methyl ester (0.400 g, 1.009 mmol), 4-fluoro-3-methylbenzaldehyde (0.139 g, 1.009 mmol), and triethylamine (0.204 g, 2.018 mmol) in 10 mL of dichloroethane, was added NaBH(OAc)3 (0.299 g, 1.413 mmol). After stirring at room temperature for 63 h, the reaction was quenched with 30 mL of saturated NaHCO3 solution and the reaction mixture was extracted with ethyl acetate (30 mL×3). The combined organic extracts dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-10% methanol/dichloromethane to give the title compound as brown oil (0.357 g, 87% yield). GC-MS: tR=7.5 min; m/z 404 (M+).

Workup

  1. customthe reaction was quenched with 30 mL of saturated NaHCO3 solution
  2. extractionthe reaction mixture was extracted with ethyl acetate (30 mL×3)
  3. dry with materialThe combined organic extracts dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe product was isolated by Flash column chromatography (silica gel column)
  7. washeluting with 0-10% methanol/dichloromethane

Sources & evidence

ORD record
ord-d0fa266b99c741b4ad731a8962266472
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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