Hydrochloric Acid → (8-Benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73030노트

반응식

HRID 73030 반응식
[CH2:1]([N:8]1[CH2:25][CH:24]([CH:26]=[CH2:27])[O:23][C:10]2([CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH:29]([O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([OH:39])=O)=[CH:35][C:34]=1[CH3:42])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(O)C.CN(C=O)C>[CH2:1]([N:8]1[CH2:25][CH:24]([CH:26]=[CH2:27])[O:23][C:10]2([CH2:11][CH2:12][N:13]([C:37]([C:36]3[CH:40]=[CH:41][C:33]([O:32][CH:29]([CH3:30])[CH3:31])=[C:34]([CH3:42])[CH:35]=3)=[O:39])[CH2:14][CH2:15]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592729354-Isopropoxy-3-methylbenzoic acidHCID 68291372Tert-butyl 10-benzyl-8-vinyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylate

생성물 1

HCID 86672478(8-Benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone수율 99%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 6228Dimethylformamide용매

실험 절차

To tert-butyl 8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (600 mg, 1.61 mmol) in ethanol (1 mL) was added HCl (4.028 mL of 4 M in dioxane, 16.11 mmol) and the reaction mixture was stirred for 30 minutes. The reaction mixture was concentrated in vacuo, then DMF (4 mL), 4-isopropoxy-3-methyl-benzoic acid (313 mg, 1.61 mmol) and HATU (613 mg, 1.61 mmol) were added and the reaction mixture was stirred for 10 minutes. Triethylamine (898 μL, 6.44 mmol) was added and the reaction mixture was stirred for 16 hours, The reaction mixture was concentrated in vacuo, diluted with DCM (5 mL), washed with 1 N aq. NaOH (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography using 0-100% EtOAc/hexanes eluent to give (8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone (715 mg, 99%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.22 (m, 5H), 7.20-7.14 (m, 2H), 6.79 (d, J=8.2 Hz, 1H), 5.83-5.74 (m, 1H), 5.34-5.26 (m, 1H), 5.15 (d, J=10.6 Hz, 1H), 4.59-4.50 (m, 1H), 4.33-4.14 (m, 2H), 3.59-3.14 (m, 7H), 2.79 (d, J=11.0 Hz, 1H), 2.56 (d, J=11.1 Hz, 1H), 2.19 (s, 3H), 1.91-1.80 (m, 2H), 1.69-1.39 (m, 2H), 1.34 (d, J=6.0 Hz, 6H); ESI-MS m/z calc. 448.6. Found 449.5 (M+1)+; Retention time: 1.48 minutes (3 min run).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. stirringthe reaction mixture was stirred for 10 minutes
  3. stirringthe reaction mixture was stirred for 16 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additiondiluted with DCM (5 mL)
  6. washwashed with 1 N aq. NaOH (2 mL) and brine (2 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-3631e90ce3224ceb96afd77885c9b1df
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828996B2

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