Dibenzylamine → 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

反応式

HRID 25678 の反応式
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]

参加物

11

反応物 5

HCID 7656DibenzylamineHCID 79177tert-Butyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 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

生成物 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収率 14.4%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-666ec7b0d6cb4e00a7d79c307aeb5fad
出典データセット
uspto-grants-2005_02
特許番号
US06858591B2

関連ノート

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