Formaldehyde → HCID 11303722, compound

HRID 28808Notes

Reaction equation

HRID 28808 reaction equation
Cl.Cl.[N:3]1([CH2:9][CH:10]([C:22]2([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=2)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH2:29]=O.O.[OH-].[Na+]>C(O)=O>[CH3:29][N:6]1[CH2:7][CH2:8][N:3]([CH2:9][CH:10]([C:22]2([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=2)[CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 14798Sodium HydroxideHCID 24895013HCID 24895013, compound

Product 1

HCID 11303722HCID 11303722, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-{2-piperazin-1-yl-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol (590 mg, 1.59 mmol) (see Example 23), in formic acid (3.1 mL) at 50° C., was treated with an aqueous solution of formaldehyde (37% in water, 1.3 mL, 1.94 mmol). The reaction was heated at 70° C. for 1.5 h, after which time the reaction was poured into water (50 mL) and basified to pH=10 with the addition of a 2 N aqueous solution of sodium hydroxide. The product was then extracted with ethyl acetate (3×20 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated to yield 442 mg (72%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol as a colorless oil. The product was dissolved in methanol (0.5 mL) and the resulting solution was treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether (2 mL). The solution was stored in the refrigerator for 16 h. The resulting precipitate was filtered and washed with diethyl ether to yield 299 mg (57%) 1-{2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C20H29F3N2O2.2.00 HCl, 458.1715; found (ESI), 387.2263.

Workup

  1. extractionThe product was then extracted with ethyl acetate (3×20 mL)
  2. dry with materialthe combined organic extracts were dried over magnesium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-c03cfc08ae8547b68944435de06d3d97
Source dataset
uspto-grants-2008_09
Patent number
US07419980B2

Reaction notes

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