1-Chloroethyl chloroformate → HCID 86751754, compound

HRID 1940561Notes

Reaction equation

HRID 1940561 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([CH2:14][O:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OC(Cl)=O)C.[NH:31]1[CH:36]=CCCC1.C[N:38](CC1C2C(=NC=CC=2)NC=1)C>ClCCl.C1(C)C=CC=CC=1>[C:16]([O:15][CH2:14][C:11]1[CH2:10][CH2:9][N:8]([CH2:1][C:2]2[C:7]3[N:38]=[CH:3][CH:4]=[CH:5][C:6]=3[NH:31][CH:36]=2)[CH2:13][CH:12]=1)(=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 5213051-Chloroethyl chloroformateHCID 53835493-(Dimethylaminomethyl)-7-azaindoleHCID 10176084TetrahydropyridineHCID 867517554-Pyridinemethanol, 1,2,3,6-tetrahydro-1-(phenylmethyl)-, 4-benzoate

Product 1

HCID 86751754HCID 86751754, compoundYield 55.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of benzoic acid 1-benzyl-1,2,3,6-tetrahydropyridin-4-ylmethyl ester (1.35 g, 4.4 mmol) in anhydrous dichloromethane (50 ml) was cooled to 0° C. and treated with a solution of 1-chloroethyl-chloroformate (0.62 ml, 5.7 mmol) in anhydrous dichloromethane (10 ml). After stirring at 0° C. for 1.5 hours, the solvent was evaporated and the residue redissolved in methanol (50 ml). This solution was stirred at reflux for two hours. The solvent was evaporated and the residue partitioned between ethyl acetate and saturated aqueous potassium carbonate solution. The organic phase was separated, dried (MgSO4) and evaporated in vacuo to afford the crude product (520 mg, 58% over two steps) as a colourless oil. A solution of the crude tetrahydropyridine (520 mg, 2.5 mmol) and 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (520 mg, 2.5 mmol) in toluene (20 ml) was stirred at reflux for 9 hours. The solvent was evaporated and the residue chromatographed with 5% methanol in dichloromethane as eluant to afford the title compound (480 mg, 55%) as a colourless solid, m.p. 126° C.; (Found: C, 72.42; H, 6.08; N, 12.15. C21H21N3O2 requires C, 72.60; H, 6.09; N, 12.10%); δH (CDCl3) 2.20-2.30 (2H, m, tetrahydropyridinyl CH2), 2.68 (2H, t, J 5.7 Hz, tetrahydropyridinyl CH2), 3.05-3.10 (2H, m, tetrahydropyridinyl CH2), 3.80 (2H, s, NCH2Ar), 5.86-5.94 (1H, m, tetrahydropyridinyl 5-H), 4.74 (2H, s, CH2O), 7.07 (1H, dd, J 7.8, 4.7 Hz, 5-H), 7.20-7.30 (1H, m, ArH), 7.38-7.45 (2H, m, ArH), 7.50-7.60 (1H, m, ArH), 8.00-8.10 (3H, m, ArH), 8.30 (1H, dd, J 4.7, 1.5 Hz, 6-H), and 9.33 (1H, s, NH); m/z (CI+, NH3) 348 (M+1)+.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe residue redissolved in methanol (50 ml)
  3. stirringThis solution was stirred
  4. temperatureat reflux for two hours
  5. customThe solvent was evaporated
  6. customthe residue partitioned between ethyl acetate and saturated aqueous potassium carbonate solution
  7. customThe organic phase was separated
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customto afford the crude product (520 mg, 58% over two steps) as a colourless oil
  11. temperatureat reflux for 9 hours
  12. customThe solvent was evaporated
  13. customthe residue chromatographed with 5% methanol in dichloromethane as eluant

Sources & evidence

ORD record
ord-3a68e8f95e0f40d0b3901308d822e09c
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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