Phenylpropanolamine → HCID 67002001, compound

HRID 1804418Notes

Reaction equation

HRID 1804418 reaction equation
C(C[C@H](O[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14]Br)=[CH:9][CH:8]=1)C)C.[CH3:16][C@H:17]([NH2:26])[C@H:18]([OH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:8]([CH2:9][C@H:10]([CH2:13][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][NH:26][C@@H:17]([CH3:16])[C@H:18]([OH:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:11][CH:12]=1)[CH3:11])[CH3:7]

Participants

5

Reactant 2

HCID 10297PhenylpropanolamineHCID 67001827HCID 67001827, compound

Product 1

HCID 67002001HCID 67002001, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A compound ethyl(R)-2-[4-(2-bromoethyl)phenoxy]propane (450 mg, 1.5 mM) and (1R,2S)-Norephedrine in DMF (5 ml) it is maintained in agitation in nitrogen atmosphere at a temperature of 70° C. for 72 hours. Then the reaction mixture is diluted with ethyl acetate, washed with a saturated solution of NaCl and dried with anhydrous Na2SO4. The solvent is removed at reduced pressure and the product is isolated from the residue by column chromatography (silica gel; mobile phase: dichloromethane/ethanol=40:1). 145 mg of ethyl (R)-2-[4-[2-((1R,2S)-1-hydroxy-1-phenylpropan-2-yl-amino)ethyl]benzyl]propane is obtained as clear yellow oil (52% of yield). [α]D=−0.6 (c 1.1, CHCl3). FT-IR (neat): 3262, 3055, 2986, 2930, 1748, 1613, 1559, 1511, 1451, 1270, 1241, 1196, 1136, 1098, 1051, 1016, 743, 703 cm−1. 1NMRs (500 MHz, CDCl3, δ): 7.32-7.22 (m, 5H, aromatic protons); 7.11-7.09 (2H, aromatic protons); 6.80-6.78 (2H, aromatic protons); 5.15-5.14 (d, 1H, J=4.0 Hz, CHOH); 4.76 (bs, 2H, OH and NH: exchanged with D2O); 4.71-4.67 (q, 1H, J=6.7 Hz, CH3CHCO); 4.22-4.18 (q, 1H, J=7.2 Hz, CH2CH3); 3.71-3.67 (q, 1H, J=7.0 Hz, CH3CHNH); 3.20-2.91 (m, 4H, CH2CH2); 1.60-1.59 (d, 3H, J=6.7 Hz, OCHCH3); 1.25-1.20 (m, 3H, CH3CH2); 0.96-0.94 (m, 3H, J=7.0 Hz, CH3CHNH). 13C NMRs (125 MHz CDCl3, δ): 172.23, 161.34, 156.25, 129.69, 128.13, 127.60, 127.17, 126.10, 125.88, 115.22, 75.80, 72.62, 72.40, 61.23, 58.98, 49.72, 48.09, 34.28, 18.51, 14.08. MS-ESI m/z (%): 372 [M+H]+ (100). MS-MS (372): 354 (100), 221 (55), 147 (24), 121 (7).

Workup

  1. washwashed with a saturated solution of NaCl
  2. dry with materialdried with anhydrous Na2SO4
  3. customThe solvent is removed at reduced pressure
  4. customthe product is isolated from the residue by column chromatography (silica gel; mobile phase: dichloromethane/ethanol=40:1)

Sources & evidence

ORD record
ord-d9790ac7c6704eb89e93e4a50865dcad
Source dataset
uspto-grants-2013_01
Patent number
US08354412B2

Reaction notes

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