Formic Acid → 1-(Azetidin-3-yl)-1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)prop-2-yn-1-ol

HRID 526867Notes

Reaction equation

HRID 526867 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([C:12]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21]([O:26][CH3:27])[C:20]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=2)=[C:19]3[Cl:39])([OH:15])[C:13]#[CH:14])[CH2:9]1)=O)(C)(C)C.C(O)=O.Cl>>[NH:8]1[CH2:11][CH:10]([C:12]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21]([O:26][CH3:27])[C:20]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([C:35]([F:38])([F:36])[F:37])=[CH:33][CH:34]=2)=[C:19]3[Cl:39])([OH:15])[C:13]#[CH:14])[CH2:9]1

Participants

4

Reactant 3

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 118006295tert-Butyl-3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxyprop-2-yn-1-yl)azetidine-1-carboxylate

Product 1

HCID 1180062791-(Azetidin-3-yl)-1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)prop-2-yn-1-ol

Conditions

Temperature
0 °C

Procedure

To a flask containing tert-butyl 3-(1-(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-hydroxyprop-2-yn-1-yl)azetidine-1-carboxylate (165 mg, 0.29 mmol, Example 8) was added formic acid (5 mL, 132.5 mmol). The solution was cooled to 0° C. and 6 N aqueous HCl (50 μL, 0.3 mmol) was added. The mixture was stirred at 0° C. for 30 minutes then allowed to warm to room temperature. After 60 minutes, the reaction mixture was quenched with MeOH (10 mL) and stirred for 15 minutes and then concentrated. The residue was passed through a short column of silica gel (5% MeOH-DCM increasing to 10% 2 M NH3 in MeOH) which afforded the title compound as a light amber solid. 1H NMR (400 MHz, CD3OD) δ 8.44 (d, J=2.0 Hz, 1H), 8.01-7.72 (m, 3H), 7.53 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 4.43-4.25 (m, 3H), 4.22-4.09 (m, 2H), 4.06 (d, J=2.2 Hz, 3H), 3.88 (t, J=9.7 Hz, 1H), 3.49-3.36 (m, 1H), 3.36 (d, J=1.9 Hz, 1H). MS (ESI): mass calcd. for C24H20ClF3N2O2, 460.1; m/z found 460.9 [M+H]+.

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 60 minutes
  3. customthe reaction mixture was quenched with MeOH (10 mL)
  4. stirringstirred for 15 minutes
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-adcea57c29a9401f88dff75b4c1675ac
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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