Trifluoroacetic acid → ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 251481ノート

反応式

HRID 251481 の反応式
[CH2:1]([O:3][C:4]([N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][CH:9]([N:14]1[CH2:19][CH2:18][C:17]3([C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]3)[CH2:16][CH2:15]1)[CH2:10]2)=[O:5])[CH3:2].FC(F)(F)C(O)=O>ClCCl.C(#N)C>[N:14]1([CH:9]2[CH2:10][CH:11]3[N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:7]([CH2:13][CH2:12]3)[CH2:8]2)[CH2:19][CH2:18][C:17]2([C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22][NH:21][CH2:20]2)[CH2:16][CH2:15]1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 58089822tert-butyl 1'-(8-(ethoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-spiro[isoquinoline-4,4'-piperidine]-2(3H)-carboxylate

生成物 1

HCID 58089661ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate収率 88.3%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

The crude tert-butyl 1′-(8-(ethoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H -spiro[isoquinoline-4,4′-piperidine]-2(3H)-carboxylate 5b (3.641 g) was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (10 mL). The reaction was stirred at room temperature for 45 min, then concentrated under reduced pressure. The oil obtained was re-dissolved in acetonitrile, re-concentrated under reduced pressure, treated with 2 N NaOH (25 mL) and extracted with dichloromethane (2×50 mL). The combined extracts were washed with saturated NaHCO3, saturated brine, dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure to afford 2.55 g crude ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate 5c as a pale yellow oil, which solidified upon standing overnight at room temperature. LC/MS m/z [M+H]+ 384.2 retention time 1.34 min (10-99% CH3CN—H2O gradient, with 0.05% TFA, 5 min). 1H-NMR (400 MHz, CDCl3) δ 7.60 (d, J=8.0 Hz, 1H), 7.29 (t, J=7.3 Hz, 1H), 7.19 (t, J=7.4 Hz, 1H), 7.07 (d, J=7.5 Hz, 1H), 6.06 (br s, 2H), 4.37 (br s, 2H), 4.25 (s, 2H), 4.12 (q, J=7.1 Hz, 2H), 3.47 (m, 3H), 3.24 (m, 2H), 2.93 (m, 2H), 2.53 (m, 2H), 1.96 (m, 8H), 1.71 (m, 2H), 1.26 (t, J=7.1 Hz, 3H).

後処理

  1. concentrationconcentrated under reduced pressure
  2. customThe oil obtained
  3. concentrationre-concentrated under reduced pressure
  4. additiontreated with 2 N NaOH (25 mL)
  5. extractionextracted with dichloromethane (2×50 mL)
  6. washThe combined extracts were washed with saturated NaHCO3, saturated brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-2329f4a275df4db0b76072d8532dcfcb
出典データセット
uspto-grants-2011_01
特許番号
US07863449B2

反応ノート

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