4-Pyrrolidinopyridine → HCID 76624916, compound

HRID 416673Notes

Reaction equation

HRID 416673 reaction equation
[O-]S(C(F)(F)F)(=O)=O.C([N+]1C=CC=CC=1Br)CC.N1(C2C=CN=CC=2)CCCC1.CCN(C(C)C)C(C)C.[CH:39]1([CH2:45][CH2:46][C:47](=O)[CH:48]([CH2:66][CH:67]2[CH2:72][CH2:71][CH2:70][CH2:69][CH2:68]2)[C:49]([N:51]([CH2:57][C:58]2[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=2)[CH:52]([CH3:56])[C:53]([OH:55])=[O:54])=[O:50])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1>C(Cl)Cl.CCOCC>[CH:39]1([CH2:45][CH2:46][C:47]23[O:54][C:53](=[O:55])[C:52]2([CH3:56])[N:51]([CH2:57][C:58]2[CH:63]=[CH:62][C:61]([O:64][CH3:65])=[CH:60][CH:59]=2)[C:49](=[O:50])[CH:48]3[CH2:66][CH:67]2[CH2:68][CH2:69][CH2:70][CH2:71][CH2:72]2)[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]1

Participants

7

Reactant 4

HCID 755674-PyrrolidinopyridineHCID 81531DiisopropylethylamineHCID 11337043HCID 11337043, compoundHCID 57609740HCID 57609740, compound

Product 1

HCID 76624916HCID 76624916, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of N-propyl-2-bromo pyridinium triflate (285 mg, 0.824 mmol) and 4-pyrrolidinopyridine (183 mg, 1.24 mmol) in CH2Cl2 (11.5 mL) was added Hünig's base (72 μL, 0.41 mmol) at 0° C. After stirring for 10 min, a solution of keto-acid 60 (200 mg, 0.412 mmol) in CH2Cl2 (5 mL) was added via syringe pump over 1 h at 0° C. The resulting suspension was stirred for 3 h at 0° C., at which point the volatiles were removed up to one-third under reduced pressure. The crude reaction mixture was diluted with Et2O (100 mL) and washed with aqueous NH4Cl solution and brine (each 30 mL). The organic layer were dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (1:10 EtOAc/hexanes) to give a mixture of two beta-lactones (60 mg, 31%, dr 1:1.6) as a colorless oil. (±)-61 (major): Rf=0.56 (20% EtOAc/hexanes); IR (neat) 1829,1701 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.22 (d, J=8.5 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.76 (d, J=15.5 Hz, 1H), 4.28 (d, J=15.0 Hz, 1H), 3.80 (s, 3H), 2.75 (t, J=7.0 Hz, 1H), 1.65-2.03 (m, 15H), 1.39 (s, 3H), 0.85-1.34 (m, 13H); 13C NMR (75 MHz, CDCl3) δ 175.0, 169.2, 159.3, 129.6, 129.4, 114.2, 86.8, 76.4, 55.4, 44.4, 42.2, 38.1, 35.0, 33.6, 33.5 (2), 33.3, 33.2, 31.7, 30.8, 26.7, 26.6, 26.3 (3), 13.0; LRMS (ESI) Calcd. for C29H41NO4 [M+H] 468, found 468. (±)-61b (minor): Rf=0.63 (20% EtOAc/hexanes); IR (neat) 1829, 1702 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.18 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 4.87 (d, J=15.5 Hz, 1H), 4.17 (d, J=15.5 Hz, 1H), 3.79 (s, 3H), 2.87 (dd, J=3.5, 11.0 Hz, 1H), 2.06 (br d, J=12.5 Hz, 1H), 1.46-1.87 (m, 12H), 1.14-1.42 (m, 12H), 0.79-1.10 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 174.3, 169.3, 159.0, 129.6, 128.9, 114.0, 87.2, 76.8, 55.2, 44.2, 43.8, 37.9, 37.4, 34.7, 34.5, 33.2, 33.0, 32.1, 30.4, 27.3, 26.5, 26.4, 26.2, 25.8, 12.3.

Workup

  1. stirringThe resulting suspension was stirred for 3 h at 0° C., at which point the volatiles
  2. customwere removed up to one-third under reduced pressure
  3. customThe crude reaction mixture
  4. washwashed with aqueous NH4Cl solution and brine (each 30 mL)
  5. dry with materialThe organic layer were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (1:10 EtOAc/hexanes)
  9. customto give

Sources & evidence

ORD record
ord-8466a9c3eb574b80b25cb094cb00f20c
Source dataset
uspto-grants-2012_01
Patent number
US08088923B2

Reaction notes

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