Acetic Acid → N-[(1S)-1-[4-[[4-(1,1-Dimethylethyl)-1-piperidinyl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide

HRID 1518981노트

반응식

HRID 1518981 반응식
Cl.[C:2]([CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)([CH3:5])([CH3:4])[CH3:3].C(N(CC)CC)C.[F:19][C:20]([F:36])([F:35])[C@@H:21]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:22]1[CH:27]=[CH:26][C:25]([CH:28]=O)=[CH:24][CH:23]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:2]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:28][C:25]2[CH:24]=[CH:23][C:22]([C@H:21]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:20]([F:35])([F:36])[F:19])=[CH:27][CH:26]=2)[CH2:8][CH2:7]1)([CH3:5])([CH3:4])[CH3:3]

참가 물질

8

반응물 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27946764-tert-butylpiperidine HydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 86691246HCID 86691246, 화합물

생성물 1

HCID 71655815N-[(1S)-1-[4-[[4-(1,1-Dimethylethyl)-1-piperidinyl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide수율 62%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Charge a five liter round-bottom flask with DCM (1.5 L) and 4-tert-butylpiperidine hydrochloride (89 g, 0.5 mol). Add triethylamine (101.4 g, 1.0 mol) to the mixture at 21° C. followed by N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)ethyl]methanesulfonamide (155 g, 0.55 mol), and acetic acid (36 g, 0.6 mol). Add sodium triacetoxyborohydride (318.6 g, 1.5 mol) portion-wise and stir the suspension at 22° C. for 15 hours. Add saturated aqueous solution of sodium bicarbonate (1800 mL) slowly with stirring until pH of the mixture is 8. Separate the organic layer and extract the aqueous layer with DCM (3×2000 mL). Dry the combined organic layers over MgSO4; filter; collect the filtrate; and concentrate the filtrate under vacuum. Purify the residue on silica gel column chromatography eluting with DCM:MeOH (100 to 95%) to provide the title compound as an off-white solid (126 g, 61.9%). MS (m/z): 407 (M+1).

후처리

  1. customat 21° C.
  2. customSeparate the organic layer
  3. extractionextract the aqueous layer with DCM (3×2000 mL)
  4. dry with materialDry the combined organic layers over MgSO4
  5. filtrationfilter
  6. customcollect the filtrate
  7. concentrationand concentrate the filtrate under vacuum
  8. customPurify the residue on silica gel column chromatography
  9. washeluting with DCM

출처 및 근거

ORD 기록
ord-ff13d3e852b04bca8c465dee29d58174
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073856B2

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