Pivaloyl chloride → 2-(4-Bromophenyl)-N-[(1R,2R)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylacetamide

HRID 2246883노트

반응식

HRID 2246883 반응식
C(Cl)(=O)C(C)(C)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11][CH:10]=1.CCN(C(C)C)C(C)C.[CH3:28][C@@H:29]([NH:38][CH3:39])[C@H:30]([OH:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl.C1COCC1>[Br:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([N:38]([C@H:29]([CH3:28])[C@H:30]([OH:37])[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH3:39])=[O:18])=[CH:13][CH:14]=1

참가 물질

6

반응물 4

HCID 62493Pivaloyl chlorideHCID 62946(-)-PseudoephedrineHCID 74654Benzeneacetic acid, 4-bromo-HCID 81531Diisopropylethylamine2회

생성물 1

HCID 670167682-(4-Bromophenyl)-N-[(1R,2R)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylacetamide

시약·촉매·용매 1

HCID 21919333Tetrahydrofurane dichloromethane용매2회

실험 절차

Pivaloyl chloride (7.8 ml, 63.3 mmol) was added dropwise to a DCM/THF solution (100 ml/20 ml) containing 4-bromophenylacetic acid (13.59 g, 63.2 mmol). DIEA (11.0 ml, 63.1 mmol) was then added dropwise (exotherm). After stirring at room temperature for 1 hour the solution was poured slowly into a DCM/THF solution (100 ml/20 ml) containing (1R,2R)-(−)-pseudoephedrine (10.5 g, 63.5 mmol) and DIEA (11.0 ml, 63.1 mmol). After stirring overnight at room temperature the solution was concentrated and the residue partitioned between EtOAc and water. The organic phase was washed with aqueous 1N NaOH (2×), aqueous 1N HCl (3×), brine and dried over MgSO4. The solution was filtered and concentrated. The oil residue was diluted with 100 ml of toluene and concentrated. The residue was then dissolved in ethyl ether and triturated with hexanes to give the title compound as a white solid. The compound is a 3:1 mixture of amide rotational isomers by proton NMR: 1H NMR (400 MHz, asterisk denotes minor rotamer, CDCl3): δ 7.42 (d, J=8.3 Hz, 2H); 7.39-7.27 (m, 5H); 7.11*(d, J=8.4 Hz, 2H); 7.04 (d, J=8.3 Hz, 2H); 4.64-4.42 (m, 1H); 4.07-3.94 (m, 1H); 3.82-3.70 (m, 1H); 2.94*(s, 3H); 3.63 (s, 2H); 2.82 (s, 3H); 1.12 (d, J=7.0 Hz, 3H); 0.86*(d, 3H, J=7.0 Hz). LC1 3.23 min. (M+H)=362

후처리

  1. stirringAfter stirring overnight at room temperature the solution
  2. concentrationwas concentrated
  3. customthe residue partitioned between EtOAc and water
  4. washThe organic phase was washed with aqueous 1N NaOH (2×), aqueous 1N HCl (3×), brine
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated
  8. additionThe oil residue was diluted with 100 ml of toluene
  9. concentrationconcentrated
  10. dissolutionThe residue was then dissolved in ethyl ether
  11. customtriturated with hexanes

출처 및 근거

ORD 기록
ord-e9b61cfb656e4e1c96283f671f37e95e
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07687534B2

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