Ethanol → HCID 86675507, compound

HRID 1853453Notes

Reaction equation

HRID 1853453 reaction equation
C(O)C.[CH3:4][O:5][C:6]1[N:11]=[CH:10][C:9](B(O)O)=[CH:8][N:7]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH:30][C:31]([C:33]2[CH:34]=[CH:35][C:36]3[CH2:37][C@H:38]4[N:50]([CH3:51])[CH2:49][CH2:48][C@@:44]5([C:45]=3[C:46]=2[OH:47])[C@@:39]4([OH:53])[CH2:40][CH2:41][C:42](=[O:52])[CH2:43]5)=[O:32])=[CH:24][CH:23]=1>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[OH:47][C:46]1[C:45]2[C@:44]34[CH2:48][CH2:49][N:50]([CH3:51])[C@@H:38]([C@:39]3([OH:53])[CH2:40][CH2:41][C:42](=[O:52])[CH2:43]4)[CH2:37][C:36]=2[CH:35]=[CH:34][C:33]=1[C:31]([NH:30][CH2:29][CH2:28][C:25]1[CH:24]=[CH:23][C:22]([C:9]2[CH:8]=[N:7][C:6]([O:5][CH3:4])=[N:11][CH:10]=2)=[CH:27][CH:26]=1)=[O:32]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 86675506HCID 86675506, compound

Product 1

HCID 86675507HCID 86675507, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a degassed mixture of ethanol and water (4:1, 20 mL) was added 2-methoxypyrimidin-5-ylboronic acid (0.67 g, 4.4 mmol), Na2CO3 (1.24 g, 11.7 mmol) and N-[2-(4-bromophenyl)ethyl]-4,14-dihydroxy-17-methyl-6-oxomorphinan-3-carboxamide (2) (1.5 g, 2.9 mmol). The reaction mixture was further degassed and then Pd(PPh3)4 (0.32 g, 0.3 mmol) added. The reaction mixture was heated in a microwave reactor at 120° C. for 25 min. and cooled. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with 1:1 brine/water (3×35 mL). The organic phase was dried over MgSO4, filtered and evaporated. The resulting residue was further purified on silica eluting with dichloromethane/methanol (9:1) to give 4,14-dihydroxy-N-{2-[4-(2-methoxypyrimidin-5-yl)phenyl]ethyl}-17-methyl-6-oxomorphinan-3-carboxamide (3) (0.50 g, 32%) as a yellow foam.

Workup

  1. customThe reaction mixture was further degassed
  2. temperaturecooled
  3. washwashed with 1:1 brine/water (3×35 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe resulting residue was further purified on silica eluting with dichloromethane/methanol (9:1)

Sources & evidence

ORD record
ord-752211b355a34acda0db9950ae34a958
Source dataset
uspto-grants-2015_02
Patent number
US08962646B2

Reaction notes

Loading…