2-Amino-2-methyl-1-propanol → HCID 49799634, compound

HRID 1399535Notes

Reaction equation

HRID 1399535 reaction equation
[CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]([Cl:12])[CH:6]=1)=[O:4].BrBr.[NH2:15][C:16]([CH3:20])([CH3:19])[CH2:17][OH:18]>C(Cl)Cl.C(OCC)C>[Cl:11][C:9]1[CH:10]=[C:5]([C:3]2([OH:4])[O:18][CH2:17][C:16]([CH3:20])([CH3:19])[NH:15][CH:2]2[CH3:1])[CH:6]=[C:7]([Cl:12])[CH:8]=1

Participants

6

Reactant 3

HCID 118072-Amino-2-methyl-1-propanolHCID 24408BromineHCID 445429591-(3,5-Dichlorophenyl)propan-1-one

Product 1

HCID 49799634HCID 49799634, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3,5-dichloropropiophenone (8m, 3.81 g, 0.0188 mol) in CH2Cl2 (28 mL) was added bromine (0.986 mL, 19.1 mmol) dropwise. The bromine was immediately consumed upon addition of each drop until the end of addition when it had a consistent brownish color, indicative of excess bromine. The reaction was immediately quenched with saturated aqueous NaHCO3, extracted three times with CH2Cl2. The organic layer was separated, combined and concentrated under reduced pressure, without drying to afford a yellow oil. The oil was dissolved in anhydrous diethyl ether (50 mL) and 2-amino-2-methyl-1-propanol (6.7 g, 0.075 mol) was added. The reaction mixture was stirred overnight and quenched with saturated aqueous NaHCO3. The aqueous layer was extracted three times with CH2Cl2, and the organic layers concentrated to afford another yellow oil. Purification by column chromatography on silica gel afforded 2.51 g (46%) of the title compound. The hemi-fumarate salt was prepared by dissolving the free base in methanol and adding 1.0 g of fumaric acid to form the title compound: mp 188-190° C.; 1H NMR (DMSO-d6) δ 7.58-7.57 (m, 1H), 7.47 (m, 2H), 6.67 (s, 0.5H), 4.09 (d, 1H, J=11.9 Hz), 3.53 (d, 1H, J=12.0 Hz), 3.41-3.37 (m, 1H), 1.53 (s, 3H), 1.28 (s, 3H), 1.02 (d, 3H, 6.6 Hz); 13C NMR (DMSO-d6) δ 134.9, 133.6, 127.7, 125.2, 94.7, 67.2, 52.5, 50.1, 25.0, 21.6, 14.6; Anal. (C15H19Cl2NO4.0.25H2O) calcd: C, 51.08; H, 5.57; N, 3.97. found: C, 51.13; H, 5.64; N, 3.90.

Workup

  1. customThe bromine was immediately consumed upon addition of each drop until the end of addition when it
  2. customThe reaction was immediately quenched with saturated aqueous NaHCO3
  3. extractionextracted three times with CH2Cl2
  4. customThe organic layer was separated
  5. concentrationconcentrated under reduced pressure
  6. customwithout drying
  7. customto afford a yellow oil
  8. customquenched with saturated aqueous NaHCO3
  9. extractionThe aqueous layer was extracted three times with CH2Cl2
  10. concentrationthe organic layers concentrated
  11. customto afford another yellow oil
  12. customPurification by column chromatography on silica gel

Sources & evidence

ORD record
ord-7e72ec2a9df64021975bf8b3cca2cb53
Source dataset
uspto-grants-2014_12
Patent number
US08906908B2

Reaction notes

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