Trifluoroacetic acid → HCID 22347512, compound

HRID 897145Notes

Reaction equation

HRID 897145 reaction equation
[N:1]1[C:10]2[NH:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH2:11][CH2:12][OH:13].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:33][C:34]1([Cl:50])[CH:36]([C:37]2[CH:42]=[CH:41][C:40](O)=[CH:39][CH:38]=2)[CH:35]1[CH2:44][C:45]([O:47]CC)=[O:46].N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(O)(C(F)(F)F)=O>C1COCC1>[Cl:33][C:34]1([Cl:50])[CH:36]([C:37]2[CH:42]=[CH:41][C:40]([O:13][CH2:12][CH2:11][C:2]3[CH:3]=[CH:4][C:5]4[CH2:6][CH2:7][CH2:8][NH:9][C:10]=4[N:1]=3)=[CH:39][CH:38]=2)[CH:35]1[CH2:44][C:45]([OH:47])=[O:46]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11367331HCID 11367331, compoundHCID 20817477HCID 20817477, compound

Product 1

HCID 22347512HCID 22347512, compoundYield 47.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-1-ethanol (0.16 g, 0.9 mmol) and Polymer bound PPh3(0.3 g, 0.9 mmol) in dry THF (6 mL) was added ethyl [2,2-dichloro-3-(4-hydroxyphenyl)cyclopropyl]acetate (0.18 g, 0.6 mmol) followed by diisopropyl azodicarboxylate (0.2 mL, 1 mmol). The reaction mixture was stirred at room temperature. After 18 hours, the reaction mixture was filtered through Celite to remove the polymer and washed with excess THF. Filtrate was concentrated. The concentrated residue in 50% acetonitrile in water (4 mL) was added LiOH (01 g). The reaction mixture was stirred 3 hours at room temperature. Reaction mixture was acidified by adding TFA and purified by reverse phase HPLC to afford 0.12 g (36%) of desired product. 1H NMR (CD3OD) δ 7.64 (d, 1H, J=8 Hz), 7.26 (d, 2H, J=8.4 Hz), 6.93 (d, 2H, J=8.8 Hz), 6.77 (d, 1H, J=7.6 Hz), 4.32 (t, 2H, J=6 Hz), 3.53 (t, 2H, J=5.6 Hz), 3.19 (t, 2H, J=6 Hz), 2.87-2.59 (m, 5 H), 2.32-2.26 (m, 1H), 2.01-1.95 (m, 2 H). HRMS calcd for C21H22N2O3 (M+H): 421.1080. found 421.1069.

Workup

  1. filtrationthe reaction mixture was filtered through Celite
  2. customto remove the polymer
  3. washwashed with excess THF
  4. concentrationFiltrate was concentrated
  5. additionThe concentrated residue in 50% acetonitrile in water (4 mL) was added LiOH (01 g)
  6. stirringThe reaction mixture was stirred 3 hours at room temperature
  7. customReaction mixture
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-7817cfc2a17b4f0c8466e0fdda716d41
Source dataset
uspto-grants-2005_07
Patent number
US06921767B2

Reaction notes

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