Ethyl chloroformate → HCID 14263023, compound

HRID 1485368Notes

Reaction equation

HRID 1485368 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20][CH3:21])=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.[Li+].CCC[CH2-].Cl[C:30]([O:32][CH2:33][CH3:34])=[O:31].[NH4+].[Cl-]>O1CCCC1.CCCCCC>[CH3:21][O:20][C:14]1[C:13]2([C:30]([O:32][CH2:33][CH3:34])=[O:31])[O:12][C:11]3=[C:6]4[C:5]52[C:17](=[CH:16][CH:15]=1)[CH:18]([CH2:19][C:7]4=[CH:8][CH:9]=[C:10]3[O:22][CH3:23])[N:2]([CH3:1])[CH2:3][CH2:4]5

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 61028n-Butyl lithiumHCID 5324289Thebaine

Product 1

HCID 14263023HCID 14263023, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1 g of thebaine 1 in 20 mL of tetrahydrofuran (THF) was placed in a flame-dried round-bottom flask, and 1.92 mL (1.5 equiv) of a 2.5 M solution of N-butyllithium in hexane was added while stirring at −78° C. under nitrogen. The mixture immediately turned deep wine-red and was stirred for 45 min at −78° C. Ethyl chloroformate (0.36 mL, 1.2 equiv) was added and the mixture was stirred for 4 h at −78° C. The color changed to orange-yellow. Saturated NH4Cl (5 mL) was then added per drop and most part of the solvent was removed under reduced pressure. The residual brown product was dissolved in chloroform, washed with brine solution, dried (Na2SO4) and concentrated. The residue was subjected to column chromatography on silica gel using dichloromethane-methanol (95:5) as the eluent to isolate 0.786 g (64% yield) of 5-carbethoxythebaine 2 as a pale yellow foam. 1H NMR (CDCl3, 400 MHz): δ 6.67 d (1H, J=8.6 Hz), 6.61 d (1H, J=8.6 Hz), 5.2 d (1H, J=6.2 Hz), 5.19 d (1H, J=6.2 Hz), 4.44-4.33 m (1H), 4.28-4.16 m (1H), 3.85 s (3H), 3.66 d (1H, J=6.2 Hz), 3.57 s (3H), 3.29 d (1H, J=17.9 Hz), 2.87-2.74 m (1H), 2.7 d (1H, J=7.0 Hz), 2.68-2.57 m (1H), 2.45 s (3H), 2.16 td (1H, J=4.6, 12.5 Hz), 1.64 d (1H, J=13.3 Hz), 1.30 t (3H, J=7.0 Hz). 13C NMR (CDCl3, 100 MHz): δ 168.31, 152.64, 143.62, 142.66, 132.30, 130.56, 127.38, 119.86, 113.44, 112.09, 97.05, 95.42, 61.80, 61.26, 56.45, 55.27, 49.09, 45.49, 42.12, 31.01, 30.42, 14.21. MS (ESI): m/z 384.1 (M+1)+.

Workup

  1. stirringThe mixture immediately turned deep wine-red and was stirred for 45 min at −78° C
  2. stirringthe mixture was stirred for 4 h at −78° C
  3. customwas removed under reduced pressure
  4. dissolutionThe residual brown product was dissolved in chloroform
  5. washwashed with brine solution
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5c6df88d5e744c7bb2cf2045864397ba
Source dataset
uspto-grants-2016_08
Patent number
US09422302B2

Reaction notes

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