Dichloromethane → (R)-2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5-(4H)-one hydrochloride

HRID 236165

반응식

HRID 236165 반응식
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:11][N:12]1[CH2:16][CH2:15][C@@H:14]([OH:17])[CH2:13]1.[H-].[Na+].CS(O)(=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)[Cl:45]>O1CCCC1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>[ClH:1].[Cl:45][CH2:16][CH2:15][C@@H:14]1[CH2:13][N:12]([CH3:11])[C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[N:10][C:2]=2[O:17]1

참가 물질

10

반응물 6

HCID 6344Dichloromethane2회HCID 6395Methanesulfonic AcidHCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 762582-Chloronicotinic acidHCID 69513321-Methyl-3-pyrrolidinol, (-)-

생성물 1

HCID 13726441(R)-2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5-(4H)-one hydrochloride

시약·촉매·용매 3

HCID 5943Carbon Tetrachloride용매HCID 8028Tetrahydrofuran용매2회HCID 8471Triethylamine용매

반응 조건

온도
25 °C

실험 절차

A solution of 47.4 g (0.3 mole) of 2-chloronicotinic acid and 30 g (0.3 mole) of (R)-1-methyl-3-pyrrolidinol in 400 ml of tetrahydrofuran was added over a period of 1 hr to a stirred suspension of 26.4 g (0.66 mole) of 60% sodium hydride/mineral oil in 500 ml of tetrahydrofuran at 55°-60° C. The mixture was stirred at reflux for 2.5 hr and allowed to cool to 25° C. About 400 ml of methylene chloride was added to the slurry followed by a dropwise addition of 34.5 g (0.36 mole) of methane sulfonic acid in 100 ml of methylene chloride. The mixture was stirred for 10 min and 157 g (0.6 mole) of triphenylphosphine was added followed by 200 ml of carbon tetrachloride. The mixture was heated to reflux for 4 hr. To the cooled (25° C.) solution was added 100 ml of triethylamine at a rapid drop. The solution was concentrated on the rotary evaporator and the residue was partitioned between methylene chloride and dilute hydrochloric acid. The methylene chloride was extracted 6 times with dilute hydrochloric acid. The acid extracts were combined, made basic with sodium hydroxide and extracted with chloroform which was dried and concentrated. The residue was dissolved in isopropyl alcohol and treated with a solution of hydrogen chloride in isopropyl alcohol. The resulting hydrochloride weighed 25 g (30%). One gram was recrystallized from isopropyl alcohol, m.p. 152°-154° C.; [α]D25 =+36.2 (water).

후처리

  1. temperatureat reflux for 2.5 hr
  2. stirringThe mixture was stirred for 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 4 hr
  5. temperatureTo the cooled (25° C.) solution
  6. concentrationThe solution was concentrated on the rotary evaporator
  7. customthe residue was partitioned between methylene chloride and dilute hydrochloric acid
  8. extractionThe methylene chloride was extracted 6 times with dilute hydrochloric acid
  9. extractionextracted with chloroform which
  10. customwas dried
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in isopropyl alcohol
  13. additiontreated with a solution of hydrogen chloride in isopropyl alcohol
  14. customOne gram was recrystallized from isopropyl alcohol, m.p. 152°-154° C.

출처 및 근거

ORD 기록
ord-ce55827a243e4282bccb4ad0e6a8da8c
출처 데이터셋
uspto-grants-1987_02
특허 번호
US04642343

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