Dimethylformamide → (+)-4-Phenyl4-[(1-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxyethoxy)methyl]-1-(2-(pyrrolidinyl)acetamido)piperidine Hydrochloride

HRID 962474

반응식

HRID 962474 반응식
[N:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:10]C([O-])=O.Cl.[C:15]1([C:21]2([CH2:27][O:28][CH:29]([C:32]3[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=3)[CH2:30][OH:31])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].C[N:53](C)C=O>CO.C(N(CC)CC)C>[ClH:10].[C:15]1([C:21]2([CH2:27][O:28][CH:29]([C:32]3[CH:37]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:35]=[C:34]([C:42]([F:45])([F:43])[F:44])[CH:33]=3)[CH2:30][OH:31])[CH2:26][CH2:25][N:24]([NH:53][C:7](=[O:9])[CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH2:23][CH2:22]2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

참가 물질

8

반응물 5

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 414564Pyrrolidin-1-ylacetic acidHCID 190847004-Phenyl-4-((1-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxyethoxy) methyl)piperidine HydrochlorideHCID 21226386Carbonochloridate

생성물 1

HCID 19084703(+)-4-Phenyl4-[(1-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxyethoxy)methyl]-1-(2-(pyrrolidinyl)acetamido)piperidine Hydrochloride

시약·촉매·용매 2

HCID 887Methanol용매HCID 8471Triethylamine용매

실험 절차

(1-Pyrrolidinyl)acetic acid (0.68 g) in dry dimethyl formamide (20 ml) was treated with triethylamine (1.38 ml) and cooled to -30° C. iButyl chloroformate (0.55 ml) was added and the reaction stirred for 10 minutes before adding the compound of Example 1 (1.0 g). The solution was allowed to warm slowly to room temperature then stirred for 16 hours. The solution was concentrated under reduced pressure then ethyl acetate was added and washed with aqueous sodium chloride, then dried and concentrated to give an oil which was dissolved in methanol and stirred with potassium carbonate for 1 hour. The solvent was evaporated and the residue partitioned between ethyl acetate and aqueous sodium chloride. The organic solution was dried (Na2SO4) and concentrated to give a residue which was purified by chromatography on neutral alumina eluting with 1% methanol/dichloromethane. The resulting product was treated with ethereal hydrogen chloride to give a white solid which was recrystallised from ethyl acetate to give the title compound; mp 110°-112° C.; MS (Cl+) 559 (M+H)+ ; 1H NMR (360 MHz, d6 -DMSO) δ 1.78-2.32 (8H, m), 2.96-3.18 (4H, m), 3.29 (1H, d, J=9.1 Hz), 3.38-3.60 (6H, m), 3.80-3.95 (1H, m), 4.24-4.33 (1 H, m), 4.38-4.47 (2H, m), 7.23 (1H. t, J=7.5 Hz), 7.34 (2H, t, J=7.5 Hz), 7.41 (2H, t, J=7.5 Hz), 7.68 (1H, s), 7.70 (1H, s) and 7.96 (1H, s).

후처리

  1. additionwas added
  2. stirringthen stirred for 16 hours
  3. concentrationThe solution was concentrated under reduced pressure
  4. additionethyl acetate was added
  5. washwashed with aqueous sodium chloride
  6. customdried
  7. concentrationconcentrated
  8. customto give an oil which
  9. customThe solvent was evaporated
  10. customthe residue partitioned between ethyl acetate and aqueous sodium chloride
  11. dry with materialThe organic solution was dried (Na2SO4)
  12. concentrationconcentrated
  13. customto give a residue which
  14. customwas purified by chromatography on neutral alumina eluting with 1% methanol/dichloromethane
  15. additionThe resulting product was treated with ethereal hydrogen chloride
  16. customto give a white solid which
  17. customwas recrystallised from ethyl acetate

출처 및 근거

ORD 기록
ord-06839cc722bc4906bfccbefaf91ac6f2
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05760018

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