Sodium Carbonate → HCID 58109371, compound

HRID 1046200Notes

Reaction equation

HRID 1046200 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[OH:7][C:8]([CH3:41])([CH3:40])[CH2:9][C@@:10]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]2[CH:24]=[CH:23][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:21][CH:20]=2)[CH3:18])[CH2:12][CH2:11]1.Cl[C:43]1[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[CH:45][N:44]=1>CN(C)C=O>[OH:7][C:8]([CH3:40])([CH3:41])[CH2:9][C@@:10]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]2[CH:20]=[CH:21][C:22]([C:43]3[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[CH:45][N:44]=3)=[CH:23][CH:24]=2)[CH3:18])[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 58109371HCID 58109371, compoundYield 105.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2 M aqueous Na2CO3 solution (1.04 mL) was added to a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-[(S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl]-1,3-oxazinan-2-one (0.50 g) and 6-chloro-nicotinonitrile (0.22 g) in dimethylformamide (3 mL). The resulting mixture was sparged with argon for 5 min, before [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) dichloromethane complex (51 mg) is added. The mixture was heated to 100° C. and stirred at this temperature overnight. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated. The residue was purified by chromatography on silica gel (CH2Cl2/MeOH 98:2->80:20) to afford (S)-6-(4-{(S)-1-[6-(2-Hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-phenyl)-nicotinonitrile as an oil (0.50 g) which was crystallized from a mixture of EtOAc (15 mL) and iPr2O (5 mL) by scratching to yield a solid, mp 160-162° C. Yield: 0.32 g (67% of theory). Mass spectrum (ESI+): m/z=456 [M+H]+. mp=160-162° C.

Workup

  1. customThe resulting mixture was sparged with argon for 5 min, before [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) dichloromethane complex (51 mg)
  2. additionis added
  3. temperatureAfter cooling to ambient temperature
  4. additionwater was added
  5. extractionthe resulting mixture was extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (CH2Cl2/MeOH 98:2->80:20)

Sources & evidence

ORD record
ord-05a017633b644bffbcfc5def6011fa02
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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