Hydrochloric Acid → 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide

HRID 1017811Notes

Reaction equation

HRID 1017811 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:15][CH2:16][NH:17][CH:18]=[O:19])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]#[C:12][CH2:13][CH3:14].C(N(CC)CC)C.C(=O)(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[Cl:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][C:47]=1[Cl:48])[CH:43]=[O:44].Cl>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[Cl:39][C:40]1[CH:41]=[C:42]([CH:43]([OH:44])[C:18]([NH:17][CH2:16][CH2:15][C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][C:11]#[C:12][CH2:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:19])[CH:45]=[CH:46][C:47]=1[Cl:48]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 227103,4-DichlorobenzaldehydeHCID 94429TriphosgeneHCID 18405780N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-formamide

Product 1

HCID 184057672-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamideYield 48%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-78 °C

Procedure

3.4 g (13.0 mmol) N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-formamide and 4.3 ml (32 mmol) triethylamine are dissolved in 13 ml CH2Cl2. 1.4 g (4.7 mmol) bis(trichloromethyl) carbonate (triphosgene) in 9 ml CH2Cl2 is added at +5° C. The mixture is stirred 4 hours at +5° C. and then cooled to −78° C. A solution of 1.43 ml (13.0 mmol) TiCl4 in 20 ml CH2Cl2 is added and the mixture is stirred for 2 hours at −40° C. 2.5 g (12.9 mmol) 3,4-dichloro-benzaldehyde in 7 ml CH2Cl2 is added dropwise and the mixture stirred for 17 hours at +20° C. The mixture is hydrolysed with 7 ml HCl 5N, stirred 30 minutes at +20° C. and washed with water. After evaporation the residue is submitted to flash-chromatography (ethyl acetate 6, hexanes 4) to give 2.7 g (48%) of the 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide. 1H-NMR (300 MHz, CDCl3): 1.15 (t, 3 H, CH2CH3), 2.22 (m, 2 H, CH2CH3), 2.75 (t, 2 H, CH2CH2), 3.51 (m, 2 H, CH2CH2), 3.69 (d, 2 H, OH), 3.83 (s, 3 H, OCH3), 4.74 (m, 2 H, OCH2), 4.96 (d, 1 H, CHOH), 6.27 (t, 1 H, NH), 6.58 (m, 1 H), 6.68 (m, 1 H), 6.92 (d, 1 H), 7.19 (d, 1 H), 7.42 (d, 1 H) and 7.49 (m, 1 H, CH arom.).

Workup

  1. stirringthe mixture is stirred for 2 hours at −40° C
  2. stirringthe mixture stirred for 17 hours at +20° C
  3. stirringstirred 30 minutes at +20° C.
  4. washwashed with water
  5. customAfter evaporation the residue

Sources & evidence

ORD record
ord-850c3f04cd704bdbb83eab2184a92db9
Source dataset
uspto-grants-2002_11
Patent number
US06479550B1

Reaction notes

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