Acetic Acid → tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoate

HRID 1174129노트

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HRID 1174129 반응식
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH:13]=O.Cl.[C:16]([O:20][C:21](=[O:28])[C@H:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:23])([CH3:19])([CH3:18])[CH3:17].C([BH3-])#N.[Na+].C(O)(=O)C>CO.C(Cl)(Cl)Cl.C(OCC)(=O)C>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][NH:23][C@@H:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:21]([O:20][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:28]

참가 물질

8

반응물 4

HCID 176Acetic AcidHCID 76201Phthalylglycine aldehydeHCID 5003444Sodium cyanoborohydrideHCID 56776989tert-butyl (2S)-2-amino-3,3-dimethylbutanoate hydrochloride

생성물 1

HCID 67407870tert-butyl(2S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3,3-dimethylbutanoate수율 64.9%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6212Chloroform용매HCID 8857Ethyl Acetate용매

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온도
25 °C

실험 절차

A solution of the product of Example 3E (9.34 g, 49.4 mmol) in methanol (33 mL) was treated with L-tert-leucine tert-butyl ester hydrochloride (10 g, 44.9 mmol), sodium cyanoborohydride (5.6 g, 89.8 mmol), and acetic acid (1.5 ml, 26.2 mmol), stirred at 25° C. for 4 hours, and partitioned between chloroform and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel, eluting with first with 66% chloroform in hexanes and then with 33% ethyl acetate in chloroform to give the title compound (10.5 g, 59% yield).

후처리

  1. custompartitioned between chloroform and saturated NaHCO3
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel
  7. washeluting with first with 66% chloroform in hexanes

출처 및 근거

ORD 기록
ord-00a8a93ce66e464f9983543c2997f649
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834043B2

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