Dichloromethane → Ammonium Hydroxide

HRID 1593039Notes

Reaction equation

HRID 1593039 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.O.O[N:17]1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.[N:37]1([C@@H:42]2[CH2:47][CH2:46][CH2:45][CH2:44][C@H:43]2[NH:48][CH3:49])[CH2:41][CH2:40][CH2:39][CH2:38]1.C(N(CC)C(C)C)(C)C.C(Cl)[Cl:60]>>[NH4+:17].[OH-:11].[ClH:60].[F:13][C:2]([F:1])([F:14])[C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([N:48]([CH3:49])[C@@H:43]2[CH2:44][CH2:45][CH2:46][CH2:47][C@H:42]2[N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[O:12])=[CH:7][CH:8]=1

Participants

8

Reactant 6

HCID 6344Dichloromethane2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 13377463Cyclohexanamine, N-methyl-2-(1-pyrrolidinyl)-, trans-

Product 2

HCID 14923Ammonium HydroxideYield 28%HCID 9887513(+/-)-trans-4-Trifluoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexy]phenylacetamide Hydrochloride

Procedure

To a solution of 4-trifluoromethylphenyl acetic acid (1.45 g, 7.08 mmol) in 10 mL of dry CH2Cl2 under a nitrogen atmosphere was added 1-hydroxybenzotriazole hydrate (HOBT) (0.95 g, 7.08 mmol) and stirred. The reaction mixture was cooled to 0→4 5° C. and solid EDCI ([1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide HCl]) (1.35 g, 7.08 mmol) was added and stirred at this temperature for 30 mm. A solution of (±) 3 (1.0 g, 5.48 mmol) in 10 mL of dry CH2Cl2 was added followed by N,N-diisopropylethylamine (Hunig's Base) (0.915 g, 7.08 mmol). The reaction mixture was stirred for 24 h while warming to room temperature. The reaction mixture was then poured onto excess of ice-cold saturated aqueous NaHCO3 solution and stirred for 30 min. After dilution with CH2Cl2, the organic layer was separated, washed with saturated salt solution, and dried over anhydrous Na2SO4. Removal of solvent gave a brown oil which was chromatographed on a silica gel column [solvent system: CH2Cl2:CH2OH:28% NH4OH (99:1:2) to give the desired product as free base. The hydrochloride salt was prepared from 1M etherial HCl and recrystallized from CH2CL2:Et20 (1:1) to give (±) 5g HCl as a cream colored solid, 0.68 g (30%); 213-215° C.; 1H NMR (200 MHz, CDCl3) δ 1.02-1.47 (m, 4H), 1.52-2.22 (m, 8H), 2.75-2.90 (m, 2H), 2.94 (s, 3H), 3.07 (m, 1H), 3.37 (m, 1H), 3.62 (d, J=15.0 Hz, 1H), 3.77 (m, 1H), 4.17 (d, J=15.0 Hz, 1H), 4.57 (m, 1H), 7.30 (d, J=8.0 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H). Anal. Calcd for C20H27F3N2O.HCl.0.25H2O: C, 58.68; H, 7.02; N, 6.84. Found: C, 58.68; H, 6.84; N, 6.69.

Workup

  1. additionwas added
  2. stirringstirred at this temperature for 30 mm
  3. stirringThe reaction mixture was stirred for 24 h
  4. additionThe reaction mixture was then poured onto excess of ice-cold saturated aqueous NaHCO3 solution
  5. stirringstirred for 30 min
  6. customAfter dilution with CH2Cl2, the organic layer was separated
  7. washwashed with saturated salt solution
  8. dry with materialdried over anhydrous Na2SO4
  9. customRemoval of solvent
  10. customgave a brown oil which
  11. customwas chromatographed on a silica gel column [solvent system

Sources & evidence

ORD record
ord-ffe9d71d1ef34f45b2d90e924ca73db2
Source dataset
uspto-grants-2007_11
Patent number
US07294647B2

Reaction notes

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