Dimethylformamide → 4-(4-{(S)-1-[(S)-6-(2-Hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 80952Notes

Reaction equation

HRID 80952 reaction equation
CN(C)C=O.Br[C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([N:15]2[CH2:20][CH2:19][C@:18]([CH2:27][C:28]([OH:31])([CH3:30])[CH3:29])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:17][C:16]2=[O:32])[CH3:14])=[CH:9][CH:8]=1.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C([O-])([O-])=O.[K+].[K+]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[C:33]([O:37][C:38]([N:40]1[CH2:41][CH:42]=[C:43]([C:7]2[CH:12]=[CH:11][C:10]([C@@H:13]([N:15]3[CH2:20][CH2:19][C@:18]([CH2:27][C:28]([OH:31])([CH3:29])[CH3:30])([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:17][C:16]3=[O:32])[CH3:14])=[CH:9][CH:8]=2)[CH2:44][CH2:45]1)=[O:39])([CH3:36])([CH3:34])[CH3:35]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 581097264-(4-{(S)-1-[(S)-6-(2-Hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

N,N-Dimethylformamide (5 mL) was added to a flask charged with a stir bar, 3-[(S)-1-(4-bromo-phenyl)-ethyl]-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (0.30 g), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.22 g), K2CO3 (0.29 g), and [1,1′-bis(diphenylphosphino)-ferrocene]-dichloropalladium(II) (57 mg) under argon atmosphere. The resulting mixture was stirred at 80° C. 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 (cyclohexane/ethyl acetate 40:60→0:100) to afford the title compound.

Workup

  1. additioncharged with a stir bar
  2. temperatureAfter cooling to ambient temperature
  3. extractionthe resulting mixture was extracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 40:60→0:100)

Sources & evidence

ORD record
ord-b7c2db829f054937893e9ac2329cc114
Source dataset
uspto-grants-2014_09
Patent number
US08846668B2

Reaction notes

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