4-Methylmorpholine → (R)-benzyl (1-((2,2-dimethoxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate

HRID 1521481ノート

反応式

HRID 1521481 の反応式
[C:1]([NH:11][C@@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN1CCOCC1.[NH2:26][CH2:27][C:28]([O:32][CH3:33])([O:30][CH3:31])C>C1COCC1>[CH3:31][O:30][CH:28]([O:32][CH3:33])[CH2:27][NH:26][C:16](=[O:18])[C@H:12]([NH:11][C:1](=[O:2])[O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)[CH:13]([CH3:14])[CH3:15]

参加物

5

反応物 3

HCID 79724-MethylmorpholineHCID 712434N-alpha-Benzyloxycarbonyl-D-valineHCID 149002072,2-Dimethoxypropan-1-amine

生成物 1

HCID 89827923(R)-benzyl (1-((2,2-dimethoxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate収率 99.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-15 °C

実験手順

A solution of Cbz-D-Valine (500 g, 1.99 mol) and N-methylmorpholine (201.8 g, 1.99 mol) in anhydrous THF (8 L) was cooled to −15° C., i-butylchlorofomate (299 g, 2.19 mol) was added dropwise under stirring. After 30 min, a solution of 1-amino-2,2-dimethyoxypropane (209.5 g, 1.99 mol) in THF (1 L) was added slowly and the temperature was maintained at −15° C. for 2 h. The reaction mixture was washed with brine (2 L) and the organic phase was concentrated to remove the THF. The residue was diluted with EtOAc (4 L), washed with 1N aqueous HCl (2×2 L), washed with sat. NaHCO3 (2 L) and Na2CO3 (2 L), and washed with brine (1.5 L). After drying over Na2SO4, the organic solvent was removed under reduce pressure to afford (R)-benzyl (1-((2,2-dimethoxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate as a white solid (670 g, yield 99.5%), which was used for next step without further purification. LC-MS m/z 360.9 [M+Na]+. 1H NMR (CD3OD 300 MHz): δ 7.35-7.30 (m, 5H), 5.08 (s, 2H), 4.45-4.35 (m, 1H), 3.95-3.85 (m, 1H), 3.34-3.25 (m, 8H), 2.10-1.90 (m, 1H), 0.94-0.91 (m, 6H).

後処理

  1. additioni-butylchlorofomate (299 g, 2.19 mol) was added dropwise
  2. washThe reaction mixture was washed with brine (2 L)
  3. concentrationthe organic phase was concentrated
  4. customto remove the THF
  5. additionThe residue was diluted with EtOAc (4 L)
  6. washwashed with 1N aqueous HCl (2×2 L)
  7. washwashed with sat. NaHCO3 (2 L) and Na2CO3 (2 L)
  8. washwashed with brine (1.5 L)
  9. dry with materialAfter drying over Na2SO4
  10. customthe organic solvent was removed

出典と根拠

ORDレコード
ord-02b7259e8deb4d0587b0cec3f219dd30
出典データセット
uspto-grants-2015_07
特許番号
US09073931B2

反応ノート

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