Benzaldehyde → HCID 46197829, compound

HRID 2195014Notes

Reaction equation

HRID 2195014 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[NH:16][C:17]([NH:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=1)=[S:18].[BH4-].[Na+].[NH4+].[Cl-].[NH4+].[OH-]>CO>[CH2:1]([NH:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[NH:16][C:17]([NH:19][C:20]1[CH:21]=[C:22]([C:30]([F:31])([F:32])[F:33])[CH:23]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:25]=1)=[S:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 44178464HCID 44178464, compound

Product 1

HCID 46197829HCID 46197829, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In the second step, as shown in FIG. 5, benzaldehyde (0.578 mL, 5.45 mmol, 1.05 equiv) was added to a solution of 1-((1R,2R)-2-aminocyclohexyl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea (2 g, 5.19 mmol, 1.0 equiv) in anhydrous MeOH (15 mL) under argon at rt. The resulting solution was stirred at rt for 4 hours, then cooled to 0° C. and NaBH4 (211 mg, 5.71 mmol, 1.1 equiv) was added. The reaction mixture was stirred for 20 min and saturated NH4Cl solution (50 mL) was added, followed by NH4OH (2 mL). The resulting mixture was stirred for additional 20 min, then extracted with dichloromethane (100 mL×5), dried over Na2SO4, and evaporated to dryness. The residue was purified by flash chromatography on silica gel using Hexanes/EtOAc/MeOH/NH4OH (400:100:5:1) to afford 1-((1R,2R)-2-(benzylamino)cyclohexyl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea (2.02 g, 82% yield) as pale yellow foam. The product was recrystallized from Hexanes/DCM in 75% yield as a white solid. mp 140° C.-141° C.; Rf˜0.48 (DCM/MeOH, 9:1); 1H NMR (CDCl3, 300 MHz) δ=7.69 (s, 2H), 7.48 (s, 1H), 7.29-7.20 (m, 5H), 6.59 (br s, 1H), AB (δ=3.97, 3.82, JAB=12.3 Hz), 3.44 (br s, 1H), 2.49-2.42 (m, 1H), 2.18-2.00 (m, 2H), 1.90-1.75 (m, 2H), 1.40-1.20 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ=183.3, 141.8, 138.0, 131.5 (q, JCF=30 Hz), 129.1, 128.6, 128.3, 128.1, 125.0, 122.4, 121.4, 117.1, 64.4, 62.5, 54.7, 33.2, 32.6, 24.9, 24.6; HRMS (FAB, NBA) Calcd. for C22H24N3SF6 [MH+] m/z 476.1595, found 476.1598.

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe reaction mixture was stirred for 20 min
  3. stirringThe resulting mixture was stirred for additional 20 min
  4. extractionextracted with dichloromethane (100 mL×5)
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-fb889d692dcf424ab465a50b55a98836
Source dataset
uspto-grants-2012_12
Patent number
US08334405B2

Reaction notes

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