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

반응식

HRID 25678 반응식
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]

참가 물질

11

반응물 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

생성물 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-propanoate수율 14.4%

시약·촉매·용매 4

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-666ec7b0d6cb4e00a7d79c307aeb5fad
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06858591B2

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