Diethyl Ether → 3-(7'-Amino-1', 2'-dihydro-2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-5-fluoro-benzonitrile

HRID 7005

反応式

HRID 7005 の反応式
[N+:1]([C:4]1[CH:5]=[C:6]([C:19]2[CH:20]=[C:21]([CH:24]=[C:25]([F:27])[CH:26]=2)[C:22]#[N:23])[CH:7]=[C:8]2[C:12]=1[NH:11][C:10](=[O:13])[C:9]12[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)([O-])=O.O.O.[Sn](Cl)Cl.CCOCC>C(O)(=O)C.Cl>[NH2:1][C:4]1[CH:5]=[C:6]([C:19]2[CH:20]=[C:21]([CH:24]=[C:25]([F:27])[CH:26]=2)[C:22]#[N:23])[CH:7]=[C:8]2[C:12]=1[NH:11][C:10](=[O:13])[C:9]12[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

参加物

6

反応物 3

HCID 3283Diethyl EtherHCID 61436Stannous chloride dihydrateHCID 220193243-(7'-nitro-1', 2'-dihydro-2'-oxospiro-[cyclohexane-1,3'-[3H]indol]-5'-yl)-5-fluorobenzonitrile

生成物 1

HCID 220193773-(7'-Amino-1', 2'-dihydro-2'-oxospiro[cyclohexane-1,3'-[3H]indol]-5'-yl)-5-fluoro-benzonitrile収率 52.2%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 313Hydrochloric Acid溶媒2 回

実験手順

To a solution of 3-(7′-nitro-1′,2′-dihydro-2′-oxospiro-[cyclohexane-1,3′-[3H]indol]-5′-yl)-5-fluorobenzonitrile (1.0 eq, 0.16 g, 0.4 mmol) in glacial acetic acid (4 mL) at room temperature was added a solution of tin (11) chloride dihydrate (0.25 g, 1.1 mmol) in hydrochloric acid (2 mL). The yellow mixture was boiled for 30 min at which point the yellow color disappeared. After cooling to room temperature, 1N HCl (10 mL) and ether (20 mL) were added. The layers were separated and the aqueous phase was extracted with ether (2×20 mL). The organic layers were combined, washed sequentially with water (2×20 mL), saturated aqueous NaHCO3 (20 mL), and brine (20 mL). The solution was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluting with 40% EtOAc/hexane) to give the title compound (70 mg, 50%) as an oil which crystallized upon addition of 10% EtOAc/hexanes, mp 241–3° C. 1H NMR (DMSO-d6; 400 MHz) δ 1.50–1.75 (m, 8H), 1.82–1.95(m, 2H), 4.98 (s, 2H), 6.90 (d, 1H, J=1.8 Hz), 7.09 (d, 1H, J=1.5 Hz), 7.75 (m, 2H), 7.90 (‘s’, 1H), 9.96 (bs, 1H). MS ((+)−APCI) m/z 336 [(M+H)+]. Anal. Calcd for C20H18FN3O: C, 71.63; H, 5.41; N, 12.18. Found: C, 71.16; H, 5.58; N, 12.18.

後処理

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with ether (2×20 mL)
  3. washwashed sequentially with water (2×20 mL), saturated aqueous NaHCO3 (20 mL), and brine (20 mL)
  4. dry with materialThe solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (eluting with 40% EtOAc/hexane)

出典と根拠

ORDレコード
ord-967eab84cf294f14a5ffbf24e2df570b
出典データセット
uspto-grants-2006_08
特許番号
US07084168B2

関連ノート

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