Hydrochloric Acid → Cga-380778

HRID 2213173Notes

Reaction equation

HRID 2213173 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:13][CH2:14][NH:15][CH:16]=[O:17])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]#[CH:12].C(N(CC)CC)C.C(=O)(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[Cl:37][C:38]1[CH:45]=[CH:44][C:41]([CH:42]=[O:43])=[CH:40][CH:39]=1.Cl>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[Cl:37][C:38]1[CH:45]=[CH:44][C:41]([CH:42]([OH:43])[C:16]([NH:15][CH2:14][CH2:13][C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][C:11]#[CH:12])=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:17])=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 77264-ChlorobenzaldehydeHCID 8471TriethylamineHCID 94429TriphosgeneHCID 11379286Formamide, N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-

Product 1

HCID 11474256Cga-380778

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-78 °C

Procedure

N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-formamide (34 g, 0.14 mol) and triethylamine (34 g, 0.34 mol) are dissolved in dichloromethane (120 ml). Bis(trichloromethyl) carbonate (triphosgene, 16 g, 55 mmol) in dichloromethane (80 ml) is added at +5° C. The mixture is stirred for 4 hours at +5° C. and then cooled to −78° C. A solution of titanium tetrachloride (28 g, 0.15 mol) in dichloromethane (150 ml) is added and the mixture is stirred for 2 hours at −40° C. 4-Chlorobenzaldehyde (20 g, 0.14 mol) in dichloromethane (70 ml) is added dropwise and the mixture is stirred for 17 hours at room temperature. The mixture is hydrolyzed with 5N HCl (80 ml), stirred 30 minutes at room temperature and washed with water. After evaporation of the organic layer the residue is submitted to flash-chromatography (ethyl acetate/hexane) to give 2-(4-chloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-prop-2-ynyloxy -phenyl)-ethyl]-acetamide. 1H-NMR (300 MHz, CDCl3, δ(ppm)): 2.54 (t, 1H, CO≡CH), 2.72 (t, 2H, CH2CH2), 3.53 (t, 2H, CH2CH2), 3.84 (s, 3H, OCH3), 4.78 (m, 2H, OCH2), 4.98 (s, 1H, CHOH), 6.07 (bs, 1H, NH), 6.53–7.38 (m, 7H, CH arom.

Workup

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

Sources & evidence

ORD record
ord-858d388b694f485693a22a39583abe26
Source dataset
uspto-grants-2006_09
Patent number
US07105545B2

Reaction notes

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