Ammonium Chloride → 4-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl Ester

HRID 2428168Notes

Reaction equation

HRID 2428168 reaction equation
[Li]CCCC.Br[C:7]1[CH:20]=[CH:19][C:10]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:9][CH:8]=1.[CH3:21][O:22][C:23]([C:25]1[CH2:26][N:27]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:28][CH2:29][C:30]=1OS(C(F)(F)F)(=O)=O)=[O:24].[NH4+].[Cl-]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[CH3:21][O:22][C:23]([C:25]1[CH2:26][N:27]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:28][CH2:29][C:30]=1[C:7]1[CH:20]=[CH:19][C:10]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:9][CH:8]=1)=[O:24]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 4227167(4-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 671485964-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl EsterYield 96.5%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

BuLi (1.6M in hexanes, 27.0 mL, 43.1 mmol) was added to a sol. of (4-bromophenoxy)-tert-butyldimethylsilane (12.4 g, 43.1 mmol) in THF (300 mL) at −78° C. The mixture was stirred for 30 min at −78° C., and ZnCl2 (1M in THF, 52.4 mL, 52.4 mmol) was added. The mixture was allowed to warm to rt, and a sol. of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 12.0 g, 30.8 mmol) in THF (20 mL) and Pd(PPh3)4 (1.00 g, 0.863 mmol) were added. The mixture was stirred at rt overnight, and aq. sat. NH4Cl was added. The mixture was extracted with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:9→1:1) yielded the title compound (13.3 g, 96%). LC-MS: tR=1.20 min; ES+: 448.35.

Workup

  1. temperatureto warm to rt
  2. stirringThe mixture was stirred at rt overnight
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialextracts were dried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customPurification of the crude by FC (EtOAc/heptane 1:9→1:1)

Sources & evidence

ORD record
ord-d83c4e2923cb4198be5e2f623864cbfc
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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