Acetic Acid → 4-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

HRID 273061ノート

反応式

HRID 273061 の反応式
[NH:1]1[CH2:4][CH:3]([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:2]1.[C:21]1(=O)[CH2:24][CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH:21]1([N:1]2[CH2:4][CH:3]([CH2:5][O:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]4([C:19]#[N:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[CH:11][CH:12]=3)[CH2:2]2)[CH2:24][CH2:23][CH2:22]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 68576445HCID 68576445、化合物

生成物 1

HCID 598374294-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile収率 81.4%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 10340Sodium Carbonate溶媒

実験手順

4-[4-(azetidin-3-ylmethoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile (0.29, 0.73 mmol) was dissolved in THF (2 mL). Cyclobutanone (0.06 mL, 0.80 mmol) and acetic acid (0.042 mL, 0.73 mmol) were added. The mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.311 g, 1.47 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with 10% aqueous sodium carbonate (5 mL) then extracted with DCM (2×50 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to provide a clear oil. This was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 95:5:0.5) to provide the title compound (0.194 g, 81%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.60-1.70 (m, 2H), 1.70-1.80 (m, 2H), 1.80-1.90 (m, 2H), 1.95-2.00 (m, 2H), 2.0-2.15 (m, 2H), 2.9 (m, 1H), 3.1 (t, 2H), 3.16 (m, 1H), 3.4 (t, 2H), 3.9 (m, 2H), 4.10 (m, 4H), 6.90 (d, 2H), 7.40 (d, 2H). HRMS ESI+ m/z 327.2059 [MH]+.

後処理

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. extractionthen extracted with DCM (2×50 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a clear oil
  7. customThis was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 95:5:0.5)

出典と根拠

ORDレコード
ord-f8a3de240ae94ccca137dea9a70939fd
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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