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

HRID 1174129ノート

反応式

HRID 1174129 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6212Chloroform溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
25 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-00a8a93ce66e464f9983543c2997f649
出典データセット
uspto-grants-2010_11
特許番号
US07834043B2

反応ノート

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