Trifluoroacetic anhydride → Benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate

HRID 1184040

反応式

HRID 1184040 の反応式
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:14]([C@@H:17]1[CH2:22][C@H:21]2[C@H:19]([CH2:20]2)[N:18]1[C:23](=[O:47])[C@@H:24]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:25]12[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:33][C:27]([OH:35])([CH2:28]3)[CH2:26]1)[CH2:32]2)(=O)[NH2:15].C(OCC)(=O)C1C=CC=NC=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CO.O>[C:14]([C@@H:17]1[CH2:22][C@H:21]2[C@H:19]([CH2:20]2)[N:18]1[C:23](=[O:47])[C@@H:24]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[C:25]12[CH2:32][CH:31]3[CH2:30][CH:29]([CH2:28][C:27]([OH:35])([CH2:33]3)[CH2:26]1)[CH2:34]2)#[N:15]

参加物

8

反応物 4

HCID 9845Trifluoroacetic anhydrideHCID 11430Potassium CarbonateHCID 69188Ethyl NicotinateHCID 86703401benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate

生成物 1

HCID 86703399Benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate収率 80%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Trifluoro acetic anhydride (41.36 gm) was added to a solution of [benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo-ethyl]carbamate of formula-XV (27 gm) and ethyl nicotinate (30.6 gm) in ethyl acetate at 0-5° C. After 6 hrs water was added to the reaction. Organic phase was washed with 2N HCl solution, dried and concentrated. The crude compound obtained was dissolved in methanol, hydrolyzed with aqueous potassium carbonate (112 gm of K2CO3 in 228 ml water) for 2 hrs at 25° C. Solvent was distilled off from the reaction mass and aqueous phase extracted with ethyl acetate. Organic phase was dried and evaporated and the solid obtained was purified in THF to yield 20.8 gm (80%) of the desired product. M.P: 148-150° C., HPLC Purity: 99.5% (A), H1NMR (300 MHz, CDCl3): 1.06-1.09 (m, 2H), 1.45-1.9 (m, 12H), 2.25 (m, 2H), 2.33-2.38 (dd, 1H), 2.52-2.54 (m, 1H), 3.82-3.84 (dd, 1H), 4.5 (d, 1H), 4.99-5.04 (dd, 1H), 5.08 (s, 2H), 5.59-5.63 (d, 1H), 7.32-7.63 (m, 5H).

後処理

  1. washOrganic phase was washed with 2N HCl solution
  2. customdried
  3. concentrationconcentrated
  4. customThe crude compound obtained
  5. distillationSolvent was distilled off from the reaction mass and aqueous phase
  6. extractionextracted with ethyl acetate
  7. customOrganic phase was dried
  8. customevaporated
  9. customthe solid obtained
  10. customwas purified in THF

出典と根拠

ORDレコード
ord-cbf4916f3a504e668b0bf464fea507c9
出典データセット
uspto-grants-2014_03
特許番号
US08664443B2

関連ノート

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