Hydrochloric Acid → {1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol

HRID 423472

反応式

HRID 423472 の反応式
CCOCC.[OH:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]#[N:15])[CH2:10][CH2:9]1.[OH:16][NH:17][C:18](=N)[CH:19]([CH3:21])[CH3:20].Cl>CCOC(C)=O.[Cl-].[Cl-].[Zn+2].C(O)C>[CH3:20][CH:19]([C:18]1[N:15]=[C:14]([N:11]2[CH2:12][CH2:13][CH:8]([CH2:7][OH:6])[CH2:9][CH2:10]2)[O:16][N:17]=1)[CH3:21]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 513582894-(Hydroxymethyl)piperidine-1-carbonitrileHCID 178449908HCID 178449908、化合物

生成物 1

HCID 57930076{1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol収率 39%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 1N ZnCl2 in Et2O (60.7 mL, 60.7 mmol) was added dropwise over 15 min to a solution of 4-(hydroxymethyl)-1-piperidinecarbonitrile (7.09 g, 50.6 mmol) and N-hydroxy-2-methylpropanimidamide (6.2 g, 60.7 mmol) in EtOAc (150 mL) at ambient temperature. The reaction mixture was left at ambient temperature for 15 min, decanted, and triturated with Et2O to give a white solid. The solid was heated in a solution of concentrated HCl (15 mL) and ethanol (30 mL) for 1 h. Ethanol was removed in vacuo, and the resulting residue was charged with water (150 mL). The mixture was neutralized with Na2CO3, and extracted with CH2Cl2. The organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated. The crude product was purified by chromatography on a silica gel column using 0 to 100% EtOAc/hexane to give 4.44 g (39%) of {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methanol as a clear oil. 1H NMR (400 MHz, CDCl3): δ 4.20-4.10 (m, 2H), 3.51 (d, 2H, J=6.4 Hz), 3.07-2.97 (m, 2H), 2.90-2.75 (m, 1H), 1.85-1.75 (m, 2H), 1.76-1.62 (m, 1H), 1.36-1.19 (m, 8H); LRMS (ESI), m/z 226 (M+H).

後処理

  1. customdecanted
  2. customtriturated with Et2O
  3. customto give a white solid
  4. customEthanol was removed in vacuo
  5. additionthe resulting residue was charged with water (150 mL)
  6. extractionextracted with CH2Cl2
  7. dry with materialThe organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customThe crude product was purified by chromatography on a silica gel column

出典と根拠

ORDレコード
ord-a9b3248867754ec78c90aa810050dc82
出典データセット
uspto-grants-2012_01
特許番号
US08101634B2

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