Nitromethane → 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-1-hydroxy-2-nitroethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate

HRID 513904ノート

反応式

HRID 513904 の反応式
[CH3:1][C:2]([CH3:46])([CH2:10][C:11]([O:13][C@H:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:16]([CH2:17][CH2:18][C@:19]3([CH3:43])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:42])[CH2:21][CH2:22][C@@:23]3([CH:40]=[O:41])[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:39])[CH3:38])=[C:24]32)[C:15]1([CH3:45])[CH3:44])=[O:12])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].CC12C(C)(C)C(CC1)CC2NCCNC1CC2C(C)(C)C1(C)CC2.[C@@]12(C)C(C)(C)C(CC1)CC2=O.[N+:82]([CH3:85])([O-:84])=[O:83].CCN(C(C)C)C(C)C>O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CCCCCCC.C1(C)C=CC=CC=1.C(O)(C)(C)C>[CH3:46][C:2]([CH3:1])([CH2:10][C:11]([O:13][C@H:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:16]([CH2:17][CH2:18][C@:19]3([CH3:43])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:42])[CH2:21][CH2:22][C@@:23]3([C@@H:40]([OH:41])[CH2:85][N+:82]([O-:84])=[O:83])[CH2:35][C:34](=[O:36])[C:33]([CH:37]([CH3:38])[CH3:39])=[C:24]32)[C:15]1([CH3:44])[CH3:45])=[O:12])[C:3]([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:4]

参加物

10

反応物 5

HCID 6375NitromethaneHCID 10050Camphor, (1S)-HCID 81531DiisopropylethylamineHCID 58807527N1,N2-bis(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)ethane-1,2-diamineHCID 866904001-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-formyl-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate

生成物 1

HCID 866904021-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-1-hydroxy-2-nitroethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate収率 83%

試薬・触媒・溶媒 4

HCID 165397Cupric acetate monohydrate触媒HCID 1140Toluene溶媒2 回HCID 6386tert-Butanol溶媒HCID 8900Heptane溶媒

実験手順

The reaction was charged with 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-formyl-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate (15.75 g, 1 equiv), tert-butanol (157 ml, 10 vol) and toluene (47 ml, 3 vol) and stirred at ambient temperature. The ligand (N1,N2-bis(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)ethane-1,2-diamine, derived from (S)-camphor, 0.492 g, 0.06 equiv) and copper (II) acetate mono hydrate (0.246 g, 0.05 equiv) were added in a single portion and reaction allowed to stir at ambient temperature for at least 2.5 hours (see note 1). The reaction is charged with nitromethane (7.52 g, 5 equiv) and Hunig's base (“N,N-diisopropylethylamine”-3.82 g, 1.2 equiv) and allowed to stir at ambient temperature for approximately 5 days. (See note 2). Reaction concentrated under vacuum at bath temp of no more than 35° C. to approximately 2 vols. (See note 3). Reaction charged with toluene (236 ml, 15 vols) and concentrated under vacuum again to approx 3 vols. Additional toluene (95 ml, 3 vol) was added to achieve a final reaction volume of approx 6 vols. Heptane (158 ml, 10 vols) was added slowly of to solution. Product began to crystallize out of solution upon seeding. Reaction was allowed to stir at ambient temperature for one to two hours and solids collected by filtration and washed with 10 vols of heptane. Solids were dried to a weight of 14.3 g (83% yield). Purity of isolated solid is typically ˜90-95% with a 98/2 diastereomeric ratio favoring 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-1-hydroxy-2-nitroethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate as the major diastereomer.

後処理

  1. stirringto stir at ambient temperature for at least 2.5 hours (see note 1)
  2. stirringto stir at ambient temperature for approximately 5 days
  3. customReaction
  4. concentrationconcentrated under vacuum at bath temp of no more than 35° C. to approximately 2 vols
  5. customReaction
  6. concentrationconcentrated under vacuum again
  7. additionAdditional toluene (95 ml, 3 vol) was added
  8. customreaction volume of approx 6 vols
  9. customto crystallize out of solution
  10. customReaction
  11. stirringto stir at ambient temperature for one to two hours
  12. filtrationsolids collected by filtration
  13. washwashed with 10 vols of heptane
  14. customSolids were dried to a weight of 14.3 g (83% yield)

出典と根拠

ORDレコード
ord-fcd21fbe69924000a9fa1616c1915162
出典データセット
uspto-grants-2015_08
特許番号
US09102685B2

反応ノート

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