Hydrochloric Acid → O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine

HRID 39269

反応式

HRID 39269 の反応式
C1C2C(COC([NH:18][C@H:19]([C:44]([OH:46])=[O:45])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH2:29][CH2:30][CH:31]([P:38]([CH2:42][CH3:43])([CH2:40][CH3:41])=[O:39])[P:32]([CH2:36][CH3:37])([CH2:34][CH3:35])=[O:33])=[CH:23][CH:22]=3)=O)C3C(=CC=CC=3)C=2C=CC=1.Cl>N1CCCCC1.CN(C=O)C.O>[CH2:36]([P:32]([CH:31]([P:38]([CH2:40][CH3:41])([CH2:42][CH3:43])=[O:39])[CH2:30][CH2:29][CH2:28][O:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][C@@H:19]([C:44]([OH:46])=[O:45])[NH2:18])=[CH:26][CH:25]=1)([CH2:34][CH3:35])=[O:33])[CH3:37]

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 86762026N-(9-fluorenylmethoxycarbonyl)-O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine

生成物 1

HCID 86762025O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine収率 97.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 23501187piperidine N,N-dimethylformamide溶媒

実験手順

A solution of 84 (490 mg, 0.622 mmol) in piperidine/DMF (1:1, 4 mL) was stirred at room temperature for 45 min. After diluting with water and adjusting the pH to ˜3 by the addition of 1N HCl the aqueous layer was washed with diethyl ether (2×) then the pH was readjusted to ˜10 by the addition of 1N NaOH. The product was extracted with ethyl acetate (3×) washed with saturated aqueous NaCl and dried over Na2SO4. The crude material was purified by silica gel chromatography (0 to 10% methanol in CH2Cl2 over 10 column volumes then 10 to 20% over 5 column volumes) using a Biotage Horizon™ apparatus resulting in the colourless liquid 85 (271 mg, 77%): 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J=7.1, 6H), 1.34 (t, J=7.1, 6H), 1.43 (s, 9H), 2.04-2.17 (m, 4H), 2.37 (tt, J=5.8, 24.1, 1H), 2.77 (dd, J=7.6, 13.7, 1H), 2.97 (dd, J=5.5, 13.7, 1H), 3.55 (dd, J=5.5, 7.6, 1H), 3.94 (t, J=5.8, 2H), 4.14-4.23 (m, 8H), 6.78 (d, J=8.6, 2H), 7.10 (d, J=8.6, 2H): 31P (162 MHz, CDCl3) δ 24.76 (s, 2P).

後処理

  1. washwas washed with diethyl ether (2×)
  2. additionthe pH was readjusted to ˜10 by the addition of 1N NaOH
  3. extractionThe product was extracted with ethyl acetate (3×)
  4. washwashed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. customThe crude material was purified by silica gel chromatography (0 to 10% methanol in CH2Cl2 over 10 column volumes

出典と根拠

ORDレコード
ord-e455a51751ba446b913ba39770484f9f
出典データセット
uspto-grants-2013_09
特許番号
US08524691B2

関連ノート

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