Diisopropylethylamine → (S)-{1-[4,4-Bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-methyl-carbamic acid tert-butyl ester

HRID 990336ノート

反応式

HRID 990336 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:17])[C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[F:52][C:53]1[CH:58]=[CH:57][C:56]([CH:59]([C:64]2[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=2)[CH2:60][CH2:61][CH2:62][NH2:63])=[CH:55][CH:54]=1>CN(C=O)C.C(OCC)C>[C:1]([O:5][C:6](=[O:7])[N:8]([C@H:9]([C:14](=[O:16])[NH:63][CH2:62][CH2:61][CH2:60][CH:59]([C:56]1[CH:55]=[CH:54][C:53]([F:52])=[CH:58][CH:57]=1)[C:64]1[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=1)[CH2:10][CH:11]([CH3:12])[CH3:13])[CH3:17])([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7010555(2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}-4-methylpentanoic acidHCID 18418679HCID 18418679、化合物

生成物 1

HCID 10553025(S)-{1-[4,4-Bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-methyl-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

N-tert-Butoxycarbonyl-N-methyl-L-leucine (0.42 g, 1.7 mmol, Bachem Inc., Torrance, Calif.) was dissolved in dry DMF (5 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.90 mL, 5.2 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.66 g, 1.7 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.51 g, 1.7 mmol) was then added. After additional 30 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. Concentration in vacuo followed by drying under vacuum afforded the crude desired product which was used in the subsequent reaction without further purification.

後処理

  1. customThe resulting reaction mixture
  2. stirringAfter additional 30 minutes stirring at 0° C.
  3. customreaction mixture
  4. washthe resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine
  5. dry with materialwas dried over Na2SO4
  6. concentrationConcentration in vacuo
  7. customby drying under vacuum

出典と根拠

ORDレコード
ord-cbb43b9399a1469ab55ef64c275b33ee
出典データセット
uspto-grants-2002_10
特許番号
US06458781B1

反応ノート

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