Triphenylphosphine → HCID 86679978, compound

HRID 1915768Notes

Reaction equation

HRID 1915768 reaction equation
[N:1]([CH:4]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:7][CH:6]([OH:20])[CH2:5]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:1][CH:4]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:7][CH:6]([OH:20])[CH2:5]1

Participants

5

Reactant 2

HCID 11776TriphenylphosphineHCID 86679979HCID 86679979, compound

Product 1

HCID 86679978HCID 86679978, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-3-ol, Intermediate 18 (3.4 g, 16 mmol) in THF (40 mL) and water (8 mL), was added triphenylphosphine (1.89 g, 7.2 mmol) and the mixture was heated at 65° C. for 16 hr. The solvents were removed under reduced pressure to afford 5-amino-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-3-ol (contaminated with triphenylphosphine oxide) as a viscous oil. To this amine in DCM (40 mL), di-tert-butyl dicarbonate (4.49 g, 20.6 mmol) and DIPEA (4.78 mL, 27.4 mmol) were added and the mixture stirred at room temperature for 60 hr. The solvent was removed under reduced pressure and the residue purified by silica gel column chromatography (0-100% EtOAc/isohexane) to give tert-butyl 6-hydroxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate as a yellow oil (2.6 g). To a solution of this oil (2.6 g, 10.2 mmol) in DCM (50 mL) was added deoxo-Fluor® (50% in THF, 6.7 mL, 18.6 mmol) and the mixture was stirred at room temperature for 16 hr. The mixture was diluted with DCM (30 mL), cooled in an ice/water bath and quenched by the dropwise addition of saturated aqueous NaHCO3 (30 mL). The resulting mixture was stirred for 10 min. The organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-50% EtOAc/isohexane) gave tert-butyl 6-fluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate (1.07 g, 66% over three steps) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.14-7.97 (m, 1H), 5.04-4.46 (m, 3H), 3.96-2.99 (m, 6H), 2.42-1.64 (m, 5H), 1.70-1.22 (m, 9H).

Workup

  1. customThe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-fa54360a892b4a528562b0e16f69e604
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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