Potassium Phosphate, Tribasic → Tert-Butyl 4-{4-Chloro-2-[(1R)-1-Hydroxyethyl]Phenyl}-3,6-Dihydropyridine-1(2H)-Carboxylate

HRID 2415554

Reaction equation

HRID 2415554 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)O1.Br[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[C@H:31]([OH:33])[CH3:32].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)=[C:25]([C@H:31]([OH:33])[CH3:32])[CH:26]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 50852803(alphaR)-2-Bromo-5-chloro-alpha-methylbenzenemethanol

Product 1

HCID 68519018Tert-Butyl 4-{4-Chloro-2-[(1R)-1-Hydroxyethyl]Phenyl}-3,6-Dihydropyridine-1(2H)-CarboxylateYield 74,537.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A vigorously stirred mixture of tert-butyl 4-(4,4,5,5-tetramethyl-1,2,3-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1-4) (34.0 g, 0.110 mol), (1R)-1-(2-bromo-5-chlorophenyl)ethanol (3-4) (25.8 g, 0.110 mmol), potassium phosphate tribasic (70.0 g, 0.330 mol) and tetrakis(triphenylphosphine)palladium(0) (2.54 g, 2.20 mmol) in N,N-dimethylformamide (440 mL) was degassed via three vacuum/nitrogen ingress cycles and then heated at 100° C. for approximately 18 h. After cooling to room temperature, the reaction mixture was poured into ice/water (˜1:1) and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent) afforded 3-5 (27.7 g) as a pale yellow foam.

Workup

  1. customwas degassed via three vacuum/nitrogen ingress cycles
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was poured into ice/water (˜1:1)
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude residue by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-7b8c6b701dcf42869da8b5ebde701512
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Linked notes

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