Triphosgene → HCID 118069204, compound

HRID 920718Notes

Reaction equation

HRID 920718 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.ClC(Cl)(O[C:19](=[O:25])OC(Cl)(Cl)Cl)Cl.[F:27][C:28]1[CH:29]=[C:30]([C:34]2[C:42]([C:43]([NH2:45])=[O:44])=[C:37]3[CH2:38][NH:39][CH2:40][CH2:41][N:36]3[N:35]=2)[CH:31]=[CH:32][CH:33]=1>C1COCC1>[C:43]([C:42]1[C:34]([C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([F:27])[CH:29]=2)=[N:35][N:36]2[CH2:41][CH2:40][N:39]([C:19]([NH:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)=[O:25])[CH2:38][C:37]=12)(=[O:44])[NH2:45]

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 12682914-Amino-1-Boc-piperidineHCID 118061505HCID 118061505, compound

Product 1

HCID 118069204HCID 118069204, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 4-aminopiperidine-1-carboxylate (308 mg, 1.537 mmol) and TEA (0.536 mL, 3.84 mmol) in THF (3 mL) was added triphosgene (228 mg, 0.768 mmol) at 0° C. and stirred for 30 min. at the same temperature. A solution of Intermediate 4J (200 mg, 0.768 mmol) in THF was added and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer was washed with 10% NaHCO3 (2×5 mL), water, dried over Na2SO4, filtered and concentrated. The crude product was purified using reverse phase HPLC method to afford Intermediate 97A (300 mg, 80%) as a white solid. MS(ES): m/z=487 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.51-7.55 (m, 1H), 7.42-7.51 (m, 2H), 7.35 (bs, 1H), 7.22 (m, 1H), 7.15 (bs, 1H), 6.70 (d, J=7.53 Hz, 1H), 4.72 (s, 2H), 4.14 (t, J=4.8 Hz, 2H), 3.89 (m, 2H), 3.84 (t, J=4.4 Hz, 2H), 3.65 (m, 1H), 2.85-2.78 (m, 2H), 1.75 (m, 2H), 1.41 (s, 9H), 1.32 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 h
  2. customThe reaction mixture was quenched with water
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×5 mL) The combined organic layer
  4. washwas washed with 10% NaHCO3 (2×5 mL), water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-89850647ae2a479d8f9027754226e86f
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

Loading…