Iodine → 4-Benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester

HRID 12189

反応式

HRID 12189 の反応式
[CH2:1]([O:8][C:9](=[O:21])[C@H:10]([CH2:19][OH:20])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:23][C:24]([CH3:26])=[CH2:25].C([O-])([O-])=O.[K+].[K+].[I:33]I>CC#N.CCOC(C)=O.CCCCCC>[CH2:1]([O:8][C:9]([CH:10]1[CH2:19][O:20][C:24]([CH2:23][I:33])([CH3:25])[CH2:26][N:11]1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 807IodineHCID 11430Potassium CarbonateHCID 3577853-Bromo-2-methyl-1-propene2 回HCID 59337568N-benzyl-serine benzyl ester2 回

生成物 1

HCID 671665234-Benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester収率 64%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 21226206Ethyl acetate hexane溶媒2 回

実験手順

To a solution of N-benzyl-serine benzyl ester (Intermediate 16, 6.35 g) in 90 ml of MeCN at ambient temperature was added 3-bromo-2-methyl-propene (5.6 ml), KI (740 mg) and K2CO3 (7.7 g). The reaction mixture was stirred at ambient temperature for 72 hrs. 1 ml of 3-bromo-2-methyl-propene was added and the reaction mixture was stirred for another 15 hrs. Only a small amount of starting material remained based on TLC (1:1; EtOAc-hexane). To the resulting mixture was added 11.2 g of iodine. After 4 hrs of stirring, TLC (10% EtOAc/hexane) showed complete conversion. The reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml). The separated organic phase was washed successively with water, saturated NaHCO3 and brine, dried over MgSO4, and concentrated to dryness. The residue was purified on silica (5% EtOAc/Hexane) to give 6.65 g (yellowish oil, 64% yield, about 4:1 mixture) of compound 4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester. Major Component: 1H-NMR (300 MHz, CDCl3): δ 1.22 (s, 3H), 2.50 (d, 1H), 3.16-3.36 (m, 3H), 3.75-3.95 (m, 4H), 4.06 (dd, 1H), 5.16 (d, 1H), 5.21 (d, 1H), 7.28-7.36 (m, 10H).

後処理

  1. stirringthe reaction mixture was stirred for another 15 hrs
  2. stirringAfter 4 hrs of stirring
  3. customThe reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml)
  4. washThe separated organic phase was washed successively with water, saturated NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to dryness
  7. customThe residue was purified on silica (5% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-77e443df8e2d403b81623c641b5e9394
出典データセット
uspto-grants-2010_06
特許番号
US07727985B2

関連ノート

読み込み中…