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

HRID 423085ノート

反応式

HRID 423085 の反応式
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]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 12682251-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acid2 回HCID 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-ol2 回

生成物 1

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

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-da8e477e89834f3d867fd869493df521
出典データセット
uspto-grants-2012_01
特許番号
US08101623B2

反応ノート

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