4-Methylmorpholine → trans-7-Chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-ethanol

HRID 1804

反応式

HRID 1804 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:10](=[O:17])[C@@H:9]([CH2:18][C:19](O)=[O:20])[O:8][C@H:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[C:6]=2[CH:29]=1.CN1CCOCC1.C(Cl)(=O)OCC.[BH4-].[Na+]>O1CCCC1.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:10](=[O:17])[C@@H:9]([CH2:18][CH2:19][OH:20])[O:8][C@H:7]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[C:6]=2[CH:29]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 10048630trans-7-Chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid

生成物 1

HCID 69945756trans-7-Chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-ethanol収率 99.8%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

In 200 ml of tetrahydrofuran was dissolved 14.7 g of trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid obtained in Example 2 and 4.51 ml of N-methylmorpholine. To the solution was added 3.92 ml of ethyl chlorocarbonate at -10° C.; the mixture was then stirred for 15 minutes. After the addition of 3.86 g of sodium borohydride, 200 ml of methanol was added dropwise to the solution. The mixture was stirred for one hour at room temperature and then concentrated. After the addition of 200 ml of 1N hydrochloric acid, the concentrate was extracted with 200 ml of ethyl acetate. The organic layer was washed with a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=1:1) to yield 14.2 g of trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-ethanol as colorless crystals, m.p. 157° to 159° C.

後処理

  1. additionwas added dropwise to the solution
  2. stirringThe mixture was stirred for one hour at room temperature
  3. concentrationconcentrated
  4. additionAfter the addition of 200 ml of 1N hydrochloric acid
  5. extractionthe concentrate was extracted with 200 ml of ethyl acetate
  6. washThe organic layer was washed with a saturated sodium bicarbonate aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=1:1)

出典と根拠

ORDレコード
ord-daf4ba5367694338ab2591f41b1c75e1
出典データセット
uspto-grants-1998_03
特許番号
US05726306

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