Dicyclohexylcarbodiimide → Pentanedioic acid tert-butyl ester 3-methoxy-14-hydroxy-6,7-didehydro-4,5alpha-epoxy-17-methylmorphinan-6-yl ester

HRID 1766131Notes

Reaction equation

HRID 1766131 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].CCN(C(C)C)C(C)C.C1CCC(N=C=NC2CCCCC2)CC1.[C:48]([O:52][C:53](=[O:60])[CH2:54][CH2:55][CH2:56][C:57](O)=[O:58])([CH3:51])([CH3:50])[CH3:49]>C(#N)C.CN(C1C=CN=CC=1)C.C(O)(C(F)(F)F)=O>[CH3:23][O:22][C:10]1[CH:9]=[CH:8][C:7]2[CH2:20][C@H:19]3[N:2]([CH3:1])[CH2:3][CH2:4][C@:5]45[C:6]=2[C:11]=1[O:12][C@H:13]4[C:14]([O:15][C:57](=[O:58])[CH2:56][CH2:55][CH2:54][C:53]([O:52][C:48]([CH3:50])([CH3:49])[CH3:51])=[O:60])=[CH:16][CH2:17][C@@:18]35[OH:21]

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 5284603OxycodoneHCID 114240215-(Tert-butoxy)-5-oxopentanoic acid

Product 1

HCID 86614799Pentanedioic acid tert-butyl ester 3-methoxy-14-hydroxy-6,7-didehydro-4,5alpha-epoxy-17-methylmorphinan-6-yl esterYield 53.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

A suspension of oxycodone free base (100 mg, 0.317 mmol) in 1.5 mL of anhydrous acetonitrile was stirred for 20 min with DIEA (0.2 mL 1.15 mmol). DMAP (63 mg, 0.516 mmol) and DCC (112 mg, 0.545 mmol) were then added to the stirred suspension. After 5 min 1-2 (150 mg, 0.8 mmol) was added, the mixture stirred for 16 h at rt, and the resulting orange suspension concentrated to an oil under reduced pressure. The concentrated mixture was stirred with 6 mL of acetone for 10 min, and the precipitated DCU removed by filtration. The filtrate was concentrated to give a brown oil. HPLC analysis of the oil indicated that the primary reaction product was 1-3. The concentrated oil was subjected to reverse phase C-18 silica gel chromatography using a gradient of 25–40% acetonitrile in 0.07% aqueous TFA as eluent. Evaporation of the eluent from the fraction containing 1-3 gave 82 mg (53% yield) of a colorless oil which was greater than >99% pure 1-3 (HPLC).

Workup

  1. concentrationthe resulting orange suspension concentrated to an oil under reduced pressure
  2. stirringThe concentrated mixture was stirred with 6 mL of acetone for 10 min
  3. customthe precipitated DCU removed by filtration
  4. concentrationThe filtrate was concentrated
  5. customto give a brown oil
  6. customEvaporation of the eluent from the fraction
  7. additioncontaining 1-3

Sources & evidence

ORD record
ord-d055c7f3043a40c78c4361425a55d147
Source dataset
uspto-grants-2007_06
Patent number
US07230005B2

Reaction notes

Loading…