Triethylamine → HCID 66654592, compound

HRID 2036194Notes

Reaction equation

HRID 2036194 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][CH2:21][NH2:22].C(N(CC)CC)C.Cl.C([O:33][C:34](=[O:54])[CH2:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[CH:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47][CH2:46][NH:45]1)C>CC#N.CCOC(C)=O>[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][CH2:21][NH:22][C:2]([N:45]1[CH2:46][CH2:47][C:48]2[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:44]1[C:38]1[CH:39]=[C:40]([F:43])[CH:41]=[CH:42][C:37]=1[O:36][CH2:35][C:34]([OH:33])=[O:54])=[O:4]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 831172-(2-Chlorophenyl)ethylamineHCID 94429TriphosgeneHCID 66654555HCID 66654555, compound

Product 1

HCID 66654592HCID 66654592, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of triphosgene (20 mg, 0.07 mmol, 0.33 eq.) in MeCN (0.3 mL) at −10° C. (acetone/ice bath), a solution of 2-(2-chlorophenyl)ethylamine (33 μL, 0.22 mmol, 1.10 eq.) and triethylamine (39 μL, 0.28 mmol, 1.30 eq.) in MeCN (2 mL) was added over a period of 15 min. The mixture was stirred for an additional 30 min at 0° C. and then a solution of (±)-[4-fluoro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (73 mg, 0.20 mmol, 1.00 eq.) and triethylamine (78 μL, 0.56 mmol, 2.80 eq.) in MeCN (1 mL) was slowly added. The reaction mixture was slowly warmed to r.t. (ice bath during 30 min, then r.t.) and stirred at r.t. for 60 hours. The mixture was diluted with AcOEt, washed with water and sat. aq. NaCl soln., dried over MgSO4, filtered, and evaporated. To a solution of the crude product in DMF (0.9 mL), 1M aq. NaOH soln. (0.25 mL) was added. The solution was stirred at r.t. for 18 hours. The solution was acidified with 1M aq. HCl soln. (0.25 mL) then purified by prep. HPLC (column: Waters X-Bridge, 30×75 mm, 10 um, UV/MS, acidic conditions) to afford the title compound.

Workup

  1. temperatureThe reaction mixture was slowly warmed to r.t. (ice bath during 30 min
  2. stirringr.t.) and stirred at r.t. for 60 hours
  3. washwashed with water and sat. aq. NaCl soln
  4. dry with material, dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. addition(0.25 mL) was added
  8. stirringThe solution was stirred at r.t. for 18 hours
  9. custom(0.25 mL) then purified by prep

Sources & evidence

ORD record
ord-6a5a636db44b42b2a1ed6cfe51ab846f
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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