二苄胺 → tert-Butyl (2S,3S)-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-2-(dibenzylamino)-3-hydroxy-propanoate

HRID 25678

反应方程式

HRID 25678 反应方程式
BrCC(OC(C)(C)C)=O.C(NCC1C=CC=CC=1)C1C=CC=CC=1.[CH2:25]([N:32]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([N-]C(C)C)(C)C.[Li+].[Si:57]([O:64][C@H:65]1[C@@H:69]([O:70][Si:71]([C:74]([CH3:77])([CH3:76])[CH3:75])([CH3:73])[CH3:72])[C@H:68]([N:78]2[CH:83]=[CH:82][C:81](=[O:84])[N:80]([CH2:85][C:86]3[CH:91]=[CH:90][C:89]([O:92][CH3:93])=[CH:88][CH:87]=3)[C:79]2=[O:94])[O:67][C@H:66]1[CH:95]=[O:96])([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58]>O1CCOCC1.O1CCCC1.C(OCC)(=O)C.C(O)C>[CH2:25]([N:32]([CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[CH:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[C:60]([Si:57]([CH3:59])([CH3:58])[O:64][C@H:65]1[C@@H:69]([O:70][Si:71]([C:74]([CH3:75])([CH3:77])[CH3:76])([CH3:72])[CH3:73])[C@H:68]([N:78]2[CH:83]=[CH:82][C:81](=[O:84])[N:80]([CH2:85][C:86]3[CH:87]=[CH:88][C:89]([O:92][CH3:93])=[CH:90][CH:91]=3)[C:79]2=[O:94])[O:67][C@@H:66]1[C@@H:95]([OH:96])[C@H:33]([N:32]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])([CH3:61])([CH3:62])[CH3:63]

参与物

11

反应物 5

HCID 7656二苄胺HCID 79177溴乙酸叔丁酯HCID 2724682二异丙基氨基锂HCID 14557753tert-Butyl 2-(dibenzylamino)-propanoateHCID 86587931(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde

产物 2

HCID 14557753tert-Butyl 2-(dibenzylamino)-propanoateHCID 59065932tert-Butyl (2S,3S)-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-2-(dibenzylamino)-3-hydroxy-propanoate收率 14.4%

试剂、催化剂与溶剂 4

HCID 702乙醇溶剂HCID 8028四氢呋喃溶剂2 次HCID 8857乙酸乙酯溶剂HCID 312751,4-二氧六环溶剂

实验过程

tert-Butyl 2-(dibenzylamino)-propanoate was prepared from tert-butyl bromoacetate (10 ml, 68 mmole) and dibenzylamine (26.5 ml, 138 mmole) in 1,4-dioxane (20 ml) and abs. ethanol (25 ml), following the literature procedure (Scolastico, C. Tetrahedron Letts., 1987, 43, 2317). A solution of tert-butyl 2-(dibenzylamino)-propanoate (4.75 g, 15.23 mmole) in anhydrous tetrahydrofuran (60 ml) was cooled at −78° C. under argon. A solution of lithium diisopropylamide (7.6 ml, 15.23 mmole, 2.0 M solution in tetrahydrofuran, Aldrich) was introduced to this cooled solution over a period of 15 min, and the resulting reddish orange solution was stirred at this temperature for 1 h. A solution of 1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde (4.5 g, 7.62 mmole, obtained from Reference Example 3) in anhydrous tetrahydrofuran was added via syringe to the cooled mixture over a period of 15 min. The resulting mixture was stirred at −30° C. for 15 h under argon, and diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. The residue was chromatographed (flash column, silica gel, methylene chloride:n-hexane:methanol:diethyl ether=49:49:1:1) to give tert-butyl (2S,3S)-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-2-(dibenzylamino)-3-hydroxypropanoate (990 mg, 14.4%) as a white amorphous solid.

后处理

  1. stirringThe resulting mixture was stirred at −30° C. for 15 h under argon
  2. washThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness in vacuo
  6. customThe residue was chromatographed (flash column, silica gel, methylene chloride:n-hexane:methanol:diethyl ether=49:49:1:1)

来源与证据

ORD记录
ord-666ec7b0d6cb4e00a7d79c307aeb5fad
来源数据集
uspto-grants-2005_02
专利号
US06858591B2

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