Diethyl methylphosphonate → diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate

HRID 522166ノート

反応式

HRID 522166 の反応式
C([Li])CCC.[CH3:6][P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10].[CH2:15]([O:22][C@H:23]1[C@H:28]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:27]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:26]([CH3:45])[O:25][C:24]1=[O:46])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH2:15]([O:22][C@H:23]1[C@H:28]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:27]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C@H:26]([CH3:45])[O:25][C@@:24]1([CH2:6][P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[OH:46])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

参加物

5

反応物 3

HCID 12685Diethyl methylphosphonateHCID 10432954(3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-oneHCID 178418339Butyllithium

生成物 1

HCID 11786599diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate収率 67.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

n-Butyllithium (2.5 M in hexanes, 0.64 mL, 1.59 mmol, commercially available from Sigma Aldrich) was added to a stirred solution of diethyl methylphosphonate (0.23 mL, 1.59 mmol, commercially available from Sigma Aldrich) in THF (1.5 mL) at −78° C. under an argon atmosphere. The mixture was stirred for 15 min before a solution of (3 S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-one (0.275 g, 0.636 mmol) in THF (1 mL) at −78° C. was added. The reaction mixture was removed from the cooling bath, and the mixture was allowed to warm to room temperature while stirring for 1 h. The reaction mixture was next concentrated in vacuo. The resulting oil was purified by silica gel chromatography (0 to 75% EtOAc/hexanes gradient) to give diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate as a colorless oil (0.251 g, 67.5% yield). 1H NMR (400 MHz, CDCl3): δ ppm 1.09 (d, J=6.65 Hz, 3 H) 1.26 (q, J=6.85 Hz, 6 H) 1.76 (dd, J=18.49, 15.16 Hz, 1 H) 2.33 (dd, J=17.41, 15.26 Hz, 1 H) 3.68 (br. d, J=1.60 Hz, 1 H) 3.72 (d, J=9.98 Hz, 1 H) 3.92-4.02 (m, 2 H) 4.06-4.17 (m, 4 H) 4.69 (dd, J=11.54, 4.11 Hz, 2H) 4.77 (dd, J=16.43, 11.74 Hz, 2 H) 4.99 (dd, J=11.54, 9.39 Hz, 2 H) 7.26-7.41 (m, 15 H).

後処理

  1. customat −78° C.
  2. additionwas added
  3. customThe reaction mixture was removed from the cooling bath
  4. concentrationThe reaction mixture was next concentrated in vacuo
  5. customThe resulting oil was purified by silica gel chromatography (0 to 75% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-ac20e89193fc476f83020c36cbf7c257
出典データセット
uspto-grants-2016_05
特許番号
US09328134B2

反応ノート

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