Triethylamine → HCID 86614759, compound

HRID 333278Notes

Reaction equation

HRID 333278 reaction equation
NC[C:3]1([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[CH2:8][CH2:7][CH2:6][C:5]([CH3:10])([OH:9])[CH2:4]1.C[CH2:20][N:21](CC)CC.[O:26](C(OC(C)(C)C)=O)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>C(Cl)Cl>[Cl:18][C:13]1[CH:12]=[C:11]([C:3]2([N:21]([CH3:20])[C:27](=[O:26])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:8][CH2:7][CH2:6][C:5]([OH:9])([CH3:10])[CH2:4]2)[CH:16]=[CH:15][C:14]=1[Cl:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 58954803HCID 58954803, compound

Product 1

HCID 86614759HCID 86614759, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-aminomethyl-3-(3,4-dichloro-phenyl)-1-methyl-cyclohexanol (0.5 g, 1.74 mmoL) in CH2Cl2 (15 mL) was added Et3N (528 mg, 727 mL, 5.22 mmol) and (BOC)2O (567 mg, 2.60 mmol). The reaction mixture was stirred for 2 h at room temperature before being quenched by a saturated NH4Cl solution (10.0 mL). The product was extracted with CH2Cl2 (2×15 mL). The combined extracts were washed with saturated brine, dried and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1:5) to afford (±)tert-butyl (1-(3,4-dichlorophenyl)-3-hydroxy-3-methylcyclohexyl)-methylcarbamate (0.61 g, 90%). The enantiomers were separated (chiral AD column with hexane/iso-propanol/DEA=95:5:0.1) to afford the fast moving enantiomer E1 (0.22 g, retention time 4.085 min) and the slow moving enantiomer E2 (0.32 g, retention time 6.051 min). To a solution of the respective enantiomer E1 (200 mg, 0.52 mmol) or E2 (200 mg, 0.52 mmol) in CH2Cl2 (4 mL) was added TFA (2.0 mL). The reaction mixtures were stirred for 0.5 h before being concentrated. The mixtures were each purified by reverse phase column chromatography (CH3CN/H2O) to give the amines 193 E1 and 193 E2 in each 80% yield. 1H NMR (400 MHz, CDCl3) δ 8.32 (broad, 1H), 7.58 (d, J=2.0 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.37 (dd, J=2.0, 8.4 Hz, 1 H), 3.55 (s, 2 H), 2.15 (m, 2 H) 1.88 (m, 1H), 1.74-1.58 (m, 4 H), 1.40 (m, 1 H), 1.21 (m, 3 H); 13CNMR (100 MHz, CD3OD) δ 146.42, 132.75, 131.01, 130.83, 128.41, 125.97, 69.31, 46.48, 44.85, 40.15, 37.81, 32.81, 32.54, 30.91, 18.17; ESI MS m/z=288.4.

Workup

  1. custombefore being quenched by a saturated NH4Cl solution (10.0 mL)
  2. extractionThe product was extracted with CH2Cl2 (2×15 mL)
  3. washThe combined extracts were washed with saturated brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1:5)

Sources & evidence

ORD record
ord-1a69b1b205d148aa80c9e9f79b5c05b6
Source dataset
uspto-grants-2014_11
Patent number
US08877975B2

Reaction notes

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