Hydrochloric Acid → HCID 89964783, compound

HRID 1846206Notes

Reaction equation

HRID 1846206 reaction equation
COC1C=CC(C([NH:9][C:10]2([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[O:13][CH2:12][CH2:11]2)=O)=CC=1.Cl>>[F:29][C:26]([F:27])([F:28])[C:23]1[CH:22]=[CH:21][C:20]([C@:10]2([NH2:9])[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[O:13][CH2:12][CH2:11]2)=[CH:25][CH:24]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 89964224HCID 89964224, compound

Product 1

HCID 89964783HCID 89964783, compound

Conditions

Temperature
150 °C

Procedure

To a microwave vial with 4-methoxy-N-(4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)benzamide (2 g, 4.67 mmol) was added HCl (5 M aqueous, 20 mL, 100 mmol). The vial was sealed and heated by microwave at 150° C. for 80 min. The reaction was then concentrated in vacuo and the residue dissolved in half saturated aqueous NaHCO3 (75 mL) and DCM (50 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated to give a green oil. Purification by ISCO (40 g SiO2, 10-100% acetone in hexanes) gave racemic title compound. 4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine ( ) was separated by preparative SFC (using a AD-H (2×15 cm); mobile phase: 12% isopropanol (DEA)/CO2, at a flow rate of 60 mL/min] resulting in Peak 1 and 2 fractions with enantiomeric excess >99%).

Workup

  1. customThe vial was sealed
  2. concentrationThe reaction was then concentrated in vacuo
  3. dissolutionthe residue dissolved in half saturated aqueous NaHCO3 (75 mL) and DCM (50 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with DCM (2×50 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto give a green oil
  10. customPurification by ISCO (40 g SiO2, 10-100% acetone in hexanes)

Sources & evidence

ORD record
ord-e79313b35bd34a049613aa2ee37e5e69
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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