Diisopropylethylamine → (+/-)-1-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 2-bromo-benzyl ester

HRID 2036224Notes

Reaction equation

HRID 2036224 reaction equation
Cl.[CH2:2]([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)[CH3:3].CCN(C(C)C)C(C)C.O=C1CCC(=O)N1[O:42][C:43](=O)[O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[Br:52]>C(Cl)Cl>[Br:52][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=1[CH2:45][O:44][C:43]([N:16]1[CH2:17][CH2:18][C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:15]1[C:9]1[CH:10]=[C:11]([Cl:14])[CH:12]=[CH:13][C:8]=1[O:7][CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:25])=[O:42]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 598169N-(2-Bromobenzyloxycarbonyloxy)succinimideHCID 66653750(+/-)-[4-Chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride

Product 1

HCID 86682585(+/-)-1-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 2-bromo-benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (836 mg, 2.00 mmol, 1.0 eq.) and DIPEA (0.86 mL, 5.00 mmol, 2.5 eq.) in DCM (30 mL), carbonic acid 2-bromo-benzyl ester 2,5-dioxo-pyrrolidin-1-yl ester (787 mg, 2.40 mmol, 1.2 eq.) was added. The mixture was stirred at r.t. during 2 hours. The reaction was quenched with 1M aq. citric acid soln. (30 mL). The layers were separated. The aq. phase was extracted with DCM (3×). The comb. org. phases were dried over MgSO4, filtered, and concentrated in vacuo. To a solution of the previous mixture in EtOH (1.1 mL), conc. H2SO4 (0.10 mL) was added. The solution was stirred at r.t. during 3 hours. Water and 5% aq. NaOH soln. were added and the mixture was extracted with DCM (3×). The comb. org. phases were dried over MgSO4, filtered and concentrated in vacuo to give the desired product as a pale yellow oil.

Workup

  1. customThe reaction was quenched with 1M aq. citric acid soln
  2. customThe layers were separated
  3. extractionThe aq. phase was extracted with DCM (3×)
  4. dry with materialphases were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionTo a solution of the previous mixture in EtOH (1.1 mL), conc. H2SO4 (0.10 mL) was added
  8. stirringThe solution was stirred at r.t. during 3 hours
  9. additionwere added
  10. extractionthe mixture was extracted with DCM (3×)
  11. dry with materialphases were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-743b9d6abe45420cbf1042164f5c9c19
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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