Benzhydrylamine → 1-benzhydrylazetidin-3-ol Hydrochloride

HRID 877901

反応式

HRID 877901 の反応式
[C:1]1([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:15][CH2:16][CH:17]1[CH2:19][O:18]1>CO>[ClH:15].[CH:7]([N:8]1[CH2:19][CH:17]([OH:18])[CH2:16]1)([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

参加物

4

反応物 2

HCID 7036BenzhydrylamineHCID 7835Epichlorohydrin

生成物 1

HCID 28017261-benzhydrylazetidin-3-ol Hydrochloride収率 5.5%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A solution of diphenylmethanamine (2737 g, 15.0 mol, 1.04 equiv) in methanol (MeOH, 6 L) was treated with 2-(chloromethyl)oxirane (1330 g, 14.5 mol) from an addition funnel at ambient temperature. During the initial addition a slight endotherm was noticed. The resulting reaction mixture was stirred at room temperature for 3 days before being warmed to reflux for an additional 3 days. When TLC showed that the reaction was deemed complete, the reaction mixture was first cooled down to room temperature and then to 0-5° C. in an ice bath. The solids were collected by filtration and washed with acetone (4 L) to give the first crop of the crude desired product (1516 g). The filtrate was concentrated under reduced pressure and the resulting semisolid was diluted with acetone (1 L). This solid was then collected by filtration to give the second crop of the crude desired product (221 g). The crude product, 1-benzhydrylazetidin-3-ol hydrochloride (1737 g, 3998.7 g theoretical, 43.4% yield), was found to be sufficiently pure to be used in the subsequent reaction without further purification. 1HNMR (300 MHz, DMSO-d6) δ 12.28 (br. d, 1H), 7.7 (m, 5H), 7.49 (m, 5H), 6.38 (d, 1H), 4.72 (br. s, 1H), 4.46 (m, 1H), 4.12 (m, 2H), 3.85 (m, 2H) ppm; C16H18ClNO (MW 275.77; C16H17NO for free base, MW, 239.31), LCMS (EI) m/e 240 (M++H).

後処理

  1. additionDuring the initial addition a slight endotherm
  2. customThe resulting reaction mixture
  3. temperaturebefore being warmed
  4. temperatureto reflux for an additional 3 days
  5. temperaturethe reaction mixture was first cooled down to room temperature
  6. customto 0-5° C.
  7. filtrationThe solids were collected by filtration
  8. washwashed with acetone (4 L)
  9. customto give the first crop of the crude desired product (1516 g)
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. additionthe resulting semisolid was diluted with acetone (1 L)
  12. filtrationThis solid was then collected by filtration

出典と根拠

ORDレコード
ord-5ca7b09b328944cea6c584e5c59d558e
出典データセット
uspto-grants-2015_03
特許番号
US08987443B2

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