Hydrazine → (2S)(4R)-N-(2-Amino-4,5-dimethoxybenzoyl)-2-(tert-butyidimethylsilyloxymethyl)-4-hydroxypyrrolidine

HRID 1826109

反応式

HRID 1826109 の反応式
NN.[CH3:3][O:4][C:5]1[C:27]([O:28][CH3:29])=[CH:26][C:8]([C:9]([N:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][CH:12]2[CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[O:10])=[C:7]([N+:30]([O-])=O)[CH:6]=1.O=[Al]O[Al]=O.C(Cl)(Cl)Cl.CO>CO.[Ni]>[NH2:30][C:7]1[CH:6]=[C:5]([O:4][CH3:3])[C:27]([O:28][CH3:29])=[CH:26][C:8]=1[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[O:10]

参加物

7

反応物 4

HCID 9321Hydrazine3 回HCID 14769CorundumHCID 21584188Chloroform methanolHCID 91343842(4R)-N-(4,5-Dimethoxy-2-nitrobenzoyl)-2-(tert-butyldimethylsilyloxymethyl)-4-hydroxypyrrolidine

生成物 1

HCID 23574480(2S)(4R)-N-(2-Amino-4,5-dimethoxybenzoyl)-2-(tert-butyidimethylsilyloxymethyl)-4-hydroxypyrrolidine収率 95%

試薬・触媒・溶媒 2

HCID 935Nickel触媒3 回HCID 887Methanol溶媒3 回

実験手順

A solution of hydrazine (6.59 g, 6.40 mL, 205.5 mmol) in MeOH (110 mL) was added dropwise to a solution of the nitro-compound 35 (18.1 g, 41.1 mmol), over anti-bumping granules and Raney Ni (2.6 g) in MeOH (325 mL) and heated at reflux. After 1 hour at reflux TLC (95% CHCl3/MeOH) revealed some amine formation. The reaction mixture was treated with further Raney Ni (2.6 g) and hydrazine (6.40 mL) in MeOH (50 mL) and was heated at reflux for an additional 30 minutes at which point TLC revealed reaction completion. The reaction mixture was then treated with sufficient Raney Ni to decompose any remaining hydrazine and heated at reflux for a further 1.5 h. Following cooling to room temperature the mixture was filtered through a sinter and the resulting filtrate evaporated in vacuo. The resulting residue was then treated with CH2Cl2 (300 mL), dried (MgSO4), filtered and evaporated in vacuo to provide the amine 36 as a green oil (16.03 g, 95%): [α]22D=−116.32 (c=0.31, CHCl3); 1H NMR (270 MHz, CDCl3) (Rotamers) δ 6.70 (s, 1H), 6.28 (s, 1H), 4.51-4.49 (m, 1H), 4.36-4.34 (m, 1H), 4.06-3.77 (m, 10H), 3.61-3.50 (m, 3H), 2.23-2.21 (m, 1H), 2.01-1.98 (m, 1H), 0.89 (s, 9H), 0.04 (s, 6H); 13C NMR (67.8 MHz, CDCl3) (Rotamers) δ 170.2, 151.5, 141.2, 140.5, 112.2, 112.0, 101.1, 70.4, 62.6, 59.0, 56.9, 56.6, 55.8, 35.7, 25.9 and 25.7, 18.2, −5.4 and −5.5; MS (EI), m/z (relative intensity) 412 (M+.+2, 3), 411 (M+.+1, 10), 410 (M+., 32), 354 (6), 353 (23), 263 (3), 212 (5), 181 (11), 180 (100), 179 (3), 165 (3), 164 (6), 152 (10), 137 (4), 136 (4), 125 (5), 120 (3), 100 (3), 94 (6), 75 (9), 73 (7), 57 (3); IR (CHCl3) 3353 (br), 2953, 2930, 2857, 1623, 1594, 1558, 1517, 1464, 1435, 1404, 1260, 1234, 1215, 1175, 1119, 1060, 1005, 915, 836, 777, 755, 666 cm−1, exact mass calcd for C20H34N2O5Si m/e 410.2237, obsd m/e 410.2281.

後処理

  1. temperatureheated
  2. temperatureat reflux
  3. temperaturewas heated
  4. temperatureat reflux for an additional 30 minutes at which point TLC
  5. customreaction completion
  6. temperatureheated
  7. temperatureat reflux for a further 1.5 h
  8. filtrationwas filtered through a sinter
  9. customthe resulting filtrate evaporated in vacuo
  10. additionThe resulting residue was then treated with CH2Cl2 (300 mL)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated in vacuo

出典と根拠

ORDレコード
ord-1e8780ad2e524e21a0f76db1ff2032c8
出典データセット
uspto-grants-2006_05
特許番号
US07049311B1

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