4-Methylmorpholine → (3R,4S,5S)-tert-butyl 4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

HRID 74718

反応式

HRID 74718 の反応式
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23](O)=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH3:45][O:46][C@@H:47]([C@@H:56]([NH:61][CH3:62])[C@@H:57]([CH3:60])[CH2:58][CH3:59])[CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50]>CC1CCCO1>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:61]([CH3:62])[C@@H:56]([C@@H:57]([CH3:60])[CH2:58][CH3:59])[C@H:47]([O:46][CH3:45])[CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:24])[CH:20]([CH3:21])[CH3:22])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 688217FMOC-L-valineHCID 14730240(3r,4s,5s)-Tert-butyl 3-methoxy-5-methyl-4-(methylamino)heptanoate hydrochloride

生成物 1

HCID 86685718(3R,4S,5S)-tert-butyl 4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate収率 113.1%

試薬・触媒・溶媒 1

HCID 73012-Methyltetrahydrofuran溶媒

実験手順

To a mixture of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valine (18.53 g, 54.60 mmol, 1.3 eq.) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (9.58 g, 54.6 mmol, 1.3 eq.) in 2-methyltetrahydrofuran (118.00 mL, 0.34 M) was added N-methylmorpholine (6.52 mL, 59.1 mmol, 1.5 eq.) followed by #4 (11.80 g, 39.9 mmol, 1 eq.). After 3 hours, the reaction was quenched with water (50 mL) and stirred for 15 minutes. The aqueous layer was separated and back-extracted with 2-methyltetrahydrofuran (50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to give a colorless oil, which was purified by silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane) to give #5 (26.2 g, 91%) as a colorless foam. LC-MS (Protocol I) m/z 581.3 [M+H+] 1604.3 [M+Na+], retention time=4.993 minutes; 1H NMR (400 MHz, DMSO-d6), possibly a mixture of rotamers, characteristic major signals: δ 7.88 (d, J=7.4 Hz, 2H), 7.71 (d, J=7.4 Hz, 2H), 7.62 (d, J=8.6 Hz, 1H), 7.41 (dd, J=7.4, 7.4 Hz, 2H), 7.27-7.34 (m, 2H), 4.13-4.32 (m, 4H), 3.70-3.82 (br m, 1H), 3.24 (s, 3H), 2.92 (br s, 3H), 2.54 (dd, J=15.7, 2.4 Hz, 1H), 2.17 (dd, J=15.4, 9.4 Hz, 1H), 1.95-2.07 (m, 1H), 1.70-1.83 (br m, 1H), 1.40 (s, 9H), 0.83-0.94 (m, 9H), 0.69 (t, J=7.2 Hz, 3H).

後処理

  1. customthe reaction was quenched with water (50 mL)
  2. customThe aqueous layer was separated
  3. extractionback-extracted with 2-methyltetrahydrofuran (50 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a colorless oil, which
  9. customwas purified by silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-6880f5f967504a58b794a36642235c7d
出典データセット
uspto-grants-2014_09
特許番号
US08828401B2

関連ノート

読み込み中…