Diisopropylethylamine → (+/-)-{4-Chloro-2-[2-(2-methoxy-benzylthiocarbamoyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid

HRID 2036203Notes

Reaction equation

HRID 2036203 reaction equation
Cl.C([O:4][C:5](=[O:25])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1)C.C(N(C(C)C)C(C)C)C.[CH3:35][O:36][C:37]1[CH:46]=[CH:45][CH:44]=[CH:43][C:38]=1[CH2:39][N:40]=[C:41]=[S:42]>C(Cl)Cl>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][CH2:6][C:5]([OH:4])=[O:25])=[C:9]([CH:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][CH2:17][N:16]2[C:41](=[S:42])[NH:40][CH2:39][C:38]2[CH:43]=[CH:44][CH:45]=[CH:46][C:37]=2[O:36][CH3:35])[CH:10]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1402562-Methoxybenzyl isothiocyanateHCID 66653750(+/-)-[4-Chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride

Product 1

HCID 86682579(+/-)-{4-Chloro-2-[2-(2-methoxy-benzylthiocarbamoyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (±)-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (76 mg, 0.20 mmol, 1.0 eq.) and N-ethyldiisopropylamine (42 μL, 0.24 mmol, 1.2 eq) in DCM (2 mL), 2-methoxybenzyl isothiocyanate (36 mg, 0.20 mmol, 1.0 eq.) was added. The resulting mixture was stirred at r.t. for 19 hours. The mixture was diluted with DCM (20 mL), washed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL). The org. layer was concentrated in vacuo. The residue was dissolved in DMF (1 mL). 1M aq. NaOH soln. (0.5 mL) was added. The mixture was stirred at r.t. for 7 hours. The solution was carefully neutralized with formic acid (0.5 mL), filtered, and purified by prep. HPLC (column: Waters X-bridge, 30×75 mm, 10 um, UV/MS, acidic conditions) to give the desired acid as a white solid.

Workup

  1. washwashed with 10% aq. AcOH (2×5 mL) and with sat. aq. NaCl (1×5 mL)
  2. concentrationlayer was concentrated in vacuo
  3. dissolutionThe residue was dissolved in DMF (1 mL)
  4. addition(0.5 mL) was added
  5. stirringThe mixture was stirred at r.t. for 7 hours
  6. filtrationfiltered
  7. custompurified by prep

Sources & evidence

ORD record
ord-d548314e33bf465ba5d30e2eeeff4fc5
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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