Tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate → tert-Butyl-3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxypropyl)azetidine-1-carboxylate

HRID 526868Notes

Reaction equation

HRID 526868 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([CH:14]3[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15]3)=[O:13])[CH:10]=2)[N:5]=[C:4]([O:25][CH3:26])[C:3]=1[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1.[CH2:38]([Mg]Br)[CH3:39]>C1COCC1>[C:21]([O:20][C:18]([N:16]1[CH2:17][CH:14]([C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[C:4]([O:25][CH3:26])[C:3]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:30][CH:29]=2)=[C:2]3[Cl:1])([OH:13])[CH2:38][CH3:39])[CH2:15]1)=[O:19])([CH3:22])([CH3:24])[CH3:23]

Participants

4

Reactant 2

HCID 86715662Tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate2×HCID 178418443HCID 178418443, compound

Product 1

HCID 118006465tert-Butyl-3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxypropyl)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flask containing tert-butyl-3-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline-6-carbonyl)azetidine-1-carboxylate (250 mg, 0.47 mmol, Intermediate 13: step b) was added THF (8 mL) to give a homogeneous solution. The solution was cooled in an ice-water bath and ethylmagnesium bromide (3 M in Et2O, 0.3 mL, 0.9 mmol) was introduced. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution and extracted with EtOAc, (4×30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness to afford a colorless gum. Chromatography on silica gel (5% EtOAc-DCM increasing to 1% MeOH-DCM) provided the title compound as a white amorphous solid. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=2.0 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.60 (dd, J=8.7, 2.1 Hz, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.1 Hz, 2H), 4.35 (s, 2H), 4.16-4.08 (m, 1H), 4.07 (s, 3H), 4.00 (t, J=8.5 Hz, 1H), 3.71-3.53 (m, 2H), 3.20-3.07 (m, 1H), 2.13 (s, 1H), 1.97-1.74 (m, 2H), 1.41 (s, 9H), 0.73 (t, J=7.4 Hz, 3H); MS (ESI): mass calcd. for C29H32ClF3N2O4, 564.2, m/z found 565.3 (M+H)+.

Workup

  1. customto give a homogeneous solution
  2. temperatureThe solution was cooled in an ice-water bath
  3. customAfter 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution
  4. extractionextracted with EtOAc, (4×30 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customto afford a colorless gum

Sources & evidence

ORD record
ord-c26b43021a7e4560b8a25a232d32db66
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

Loading…