Triethylamine → HCID 11386527, compound

HRID 2103376Notes

Reaction equation

HRID 2103376 reaction equation
Cl.[F:2][C:3]([F:24])([F:23])[C:4]1[CH:5]=[C:6]([C:10]2[CH2:14][CH:13]([C:15]([N:17]3[CH2:21][CH2:20][C@H:19]([NH2:22])[CH2:18]3)=[O:16])[O:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1.[OH:25][C:26]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[N:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:26]1([OH:25])[CH2:31][CH2:30][CH:29]([NH:22][C@H:19]2[CH2:20][CH2:21][N:17]([C:15]([CH:13]3[O:12][N:11]=[C:10]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([C:3]([F:23])([F:2])[F:24])[CH:5]=4)[CH2:14]3)=[O:16])[CH2:18]2)[CH2:28][CH2:27]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 211876304-Hydroxy-4-(pyridin-2-yl)cyclohexanoneHCID 69005136HCID 69005136, compound

Product 1

HCID 11386527HCID 11386527, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S)-1-(3-[3-(trifluoromethyl)phenyl]-4,5-dihydroisoxazol-5-ylcarbonyl)pyrrolidin-3-amine hydrochloride (178 mg, 0.489 mmol) and 4-hydroxy-4-pyridin-2-yl-cyclohexanone (95.1 mg, 0.498 mmol) in methylene chloride (6 mL) was added triethylamine (50.3 mg, 0.498 mmol) and then NaBH(OAc)3 (120 mg, 0.54 mmol). After being stirred at room temperature for 2 h, the reaction mixture was neutralized with 1 N NaOH to pH 7, and extracted with ethyl acetate (2×25 mL). The organic extracts were combined, washed with saline solution (20 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel, eluting with 1% NH4OH in ethyl acetate/methanol (95/5 to 80/20). The appropriate fractions were combined and concentrated in vacuo to give two fractions of the desired compounds: peak 1 (100 mg) and peak 2 (85 mg). Both fractions were further purified by HPLC on a C18 column, eluting with 1% NH4OH in water/acetonitrile, to give peak 1 (68 mg) and peak 2 (65 mg) as white solids. Both compounds have LCMS: (M+H)+ 503.3. Peak 1 shows two peaks in a 1 to 1 ratio in a chiral analytical column. Peak 2 shows two peaks in a 1 to 10 ratio in a chiral analytical column.

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washwashed with saline solution (20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customchromatographed on silica gel
  6. washeluting with 1% NH4OH in ethyl acetate/methanol (95/5 to 80/20)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a867c3065b8f4066902763a33a1c4643
Source dataset
uspto-grants-2009_08
Patent number
US07576089B2

Reaction notes

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