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

반응식

HRID 1184040 반응식
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]

참가 물질

8

반응물 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

생성물 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]carbamate수율 80%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-cbf4916f3a504e668b0bf464fea507c9
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664443B2

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