Cesium carbonate → HCID 86618697, compound

HRID 2239376Notes

Reaction equation

HRID 2239376 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[N:3]=1.[OH:17][CH2:18][C@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].C(P(C(C)(C)C)C1C=CC=CC=1C1C(N(C)C)=CC=CC=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(Cl)Cl.O.C1(C)C=CC=CC=1>[Si:10]([O:9][CH2:8][C:4]1[N:3]=[C:2]([O:17][CH2:18][C@H:19]2[CH2:23][CH2:22][CH2:21][N:20]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:7]=[CH:6][CH:5]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 27349362-Di-tert-butylphosphino-2'-(N,N-dimethylamino)biphenyl2×HCID 11483477Pyridine, 2-bromo-6-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

Product 1

HCID 86618697HCID 86618697, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (1.0 g, 3.3 mmol, from Example 21a), tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (0.67 g, 3.3 mmol), Pd(OAc)2 (14.8 mg, 0.066 mmol), 2′-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine (28 mg, 0.083 mmol), Cs2CO3 (2.15 g, 6.6 mmol) and toluene (10 mL) were mixed, degassed and stirred at 100° C. under a nitrogen atmosphere. After 24 h, additional portions of Pd(OAc)2 (14.8 mg, 0.066 mmol) and 2′-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine (28 mg, 0.083 mmol) were added and the reaction mixture was stirred for another 24 h. H2O and DCM were added and the organic phase was separated and evaporated. The residue was purified by flash chromatography using a gradient of EtOAc/heptane to give the title compound. Yield: 604 mg (43%). 1H NMR (400 MHz, CDCl3) δ 7.56 (t, J=8.2 Hz, 1H), 7.05 (d, J=7.0 Hz, 1H), 6.58 (d, J=8.8 Hz, 1H), 4.69 (s, 2H), 4.41-4.30 (m, 1H), 4.22-4.08 (m, 2H), 3.46-3.28 (m, 2H), 2.03-1.90 (m, 3H), 1.88-1.78 (m, 1H), 1.46 (s, 9H), 0.96 (s, 9H), 0.11 (s, 6H). MS (ESI+) 445.4 (M+1Na+).

Workup

  1. customdegassed
  2. stirringthe reaction mixture was stirred for another 24 h
  3. customthe organic phase was separated
  4. customevaporated
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-1e9f9fe2e1bf48089a0f9b5e7697477d
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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