Acetic Acid → 4-[2-(4-Bromo-2-methyl-phenylamino)-ethyl]-tetrahydro-pyran-4-carboxylic acid methyl ester

HRID 391182

Reaktionsgleichung

Reaktionsgleichung von HRID 391182
[CH3:1][C:2]1[CH:8]=[C:7]([Br:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:10][O:11][C:12]([C:14]1([CH2:20][CH:21]=O)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:13].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].NC1C=CC=CC=1>ClCCCl.C(Cl)Cl.CO>[CH3:10][O:11][C:12]([C:14]1([CH2:20][CH2:21][NH:4][C:3]2[CH:5]=[CH:6][C:7]([Br:9])=[CH:8][C:2]=2[CH3:1])[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)=[O:13]

Komponenten

9

Edukt 5

HCID 176Acetic AcidHCID 6115Aniline2×HCID 114234-Bromo-2-methylanilineHCID 5049666Sodium triacetoxyborohydrideHCID 58468045methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

Produkt 1

HCID 674223094-[2-(4-Bromo-2-methyl-phenylamino)-ethyl]-tetrahydro-pyran-4-carboxylic acid methyl esterAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 111,2-DichloroethaneLösungsmittel2×HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-Methyl-4-bromo-aniline (1.20 g, 6.45 mmol) was dissolved in DCE (30 mL); to this solution was transferred a solution of 4-(2-oxo-ethyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (1.20 g, 6.44 mmol in DCE (30 mL). The flask was submerged in a water bath at rt. To this clear solution was then added acetic acid (1.2 g, 20 mmol, 3.1 equiv), followed by addition of powder NaBH(OAc)3 (24.1 g, 19.3 mmol, 3 equiv. in 2 portions under N2 at r.t. The yellowish milky suspension was stirred at r.t. overnight. LC/MS showed m/z 356/358 at t=3.955 min. along with small amount of aniline sm at 2.078 (186/188). There was no di-alkylated product detected (MW 526.47). TLC (5% of MeOH in DCM) showed no SM aldehyde, but aniline. The reaction was diluted with DCM (30 mL), cooled to ice-water bath, and quenched with an aqueous solution of 10 mL of conc. NH4OH (7.45M) in 30 mL of water. (2 M of NH4OH). The two layers were separated, and the aqueous layer was extracted with DCM (20 mL×2). The combined DCM extracts were washed with sodium bicarbonate (20 mL), and brine (20 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The product was purified on a 40-g silica gel column (0-5% B: 0-4 min; 5-15% B 4-13 min; 20% B: 13-25 min (B is 10% MeOH in DCM) to get 2.00 g (87%) of the title compound as an oil.

Aufarbeitung

  1. customThe flask was submerged in a water bath at rt
  2. customat t=3.955 min.
  3. temperaturecooled to ice-water bath
  4. customquenched with an aqueous solution of 10 mL of conc. NH4OH (7.45M) in 30 mL of water
  5. customThe two layers were separated
  6. extractionthe aqueous layer was extracted with DCM (20 mL×2)
  7. washThe combined DCM extracts were washed with sodium bicarbonate (20 mL), and brine (20 mL)
  8. dry with materialdried (anhydrous potassium carbonate)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe product was purified on a 40-g silica gel column (0-5% B
  12. custom0-4 min
  13. custom5-15% B 4-13 min

Quellen und Nachweise

ORD-Eintrag
ord-a6f03d614a6b40259fcdec5aafb003d4
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08383814B2

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