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

HRID 1512050

반응식

HRID 1512050 반응식
[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]

참가 물질

9

반응물 5

HCID 176Acetic AcidHCID 6115Aniline2회HCID 114234-Bromo-2-methylanilineHCID 5049666Sodium triacetoxyborohydrideHCID 58468045methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

생성물 1

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

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매2회HCID 887Methanol용매HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b72ef843c50d484d840b0adf46a0ea96
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217052B2

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