Diisopropylethylamine → Tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-4-hydroxybutylcarbamoyl)piperidine-1-carboxylate

HRID 423085노트

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HRID 423085 반응식
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])([C:38](O)=[O:39])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].[NH2:49][CH:50]([C:55]1[CH:60]=[CH:59][C:58]([Cl:61])=[CH:57][CH:56]=1)[CH2:51][CH2:52][CH2:53][OH:54].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CC(N(C)C)=O.CCOC(C)=O>[C:45]([O:44][C:42]([NH:41][C:35]1([C:38](=[O:39])[NH:49][CH:50]([C:55]2[CH:56]=[CH:57][C:58]([Cl:61])=[CH:59][CH:60]=2)[CH2:51][CH2:52][CH2:53][OH:54])[CH2:34][CH2:33][N:32]([C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])[CH2:37][CH2:36]1)=[O:43])([CH3:48])([CH3:47])[CH3:46]

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acid2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577503714-Amino-4-(4-chlorophenyl)butan-1-ol2회

생성물 1

HCID 57750344Tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-4-hydroxybutylcarbamoyl)piperidine-1-carboxylate수율 77%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

반응 조건

온도
60 °C

실험 절차

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (5.24 g, 13.77 mmol) was added in one portion to 1-(tert-butoxycarbonyl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylic acid (Intermediate 70) (4.31 g, 12.5 mmol), 4-amino-4-(4-chlorophenyl)butan-1-ol (Intermediate 16) (2.5 g, 12.5 mmol) and DIPEA (6.56 mL, 37.6 mmol) in DMA (62.6 mL) under nitrogen. The resulting solution was stirred at 60° C. for 3 hours and evaporated to dryness. The crude reaction mixture was dissolved in 100 mL EtOAc and then basified with saturated NaHCO3 (150 mL) and the organic fraction dried over MgSO4, filtered and evaporated to dryness. The organic fraction was purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM). Pure fractions were then evaporated to afford tert-butyl 4-(tert-butoxycarbonylamino)-4-(1-(4-chlorophenyl)-4-hydroxybutylcarbamoyl)piperidine-1-carboxylate (5.06 g, 77%) as an off-white solid.

후처리

  1. customevaporated to dryness
  2. customThe crude reaction mixture
  3. dry with materialthe organic fraction dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe organic fraction was purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM)
  7. customPure fractions were then evaporated

출처 및 근거

ORD 기록
ord-da8e477e89834f3d867fd869493df521
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101623B2

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