Benzyl chloroformate → (+/-)-1-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-6-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 2036217Notes

Reaction equation

HRID 2036217 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:26])[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][C:21]([F:25])=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1)[CH3:3].CCN(C(C)C)C(C)C.Cl[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38]>C(Cl)Cl>[CH2:40]([O:39][C:37]([N:16]1[CH2:17][CH2:18][C:19]2[C:24](=[CH:23][CH:22]=[C:21]([F:25])[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:26])=[O:38])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 66654906HCID 66654906, compound

Product 1

HCID 66656031(+/-)-1-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-6-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an-ice cooled solution of (±)-[4-chloro-2-(6-fluoro-1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (900 mg, 2.25 mmol, 1.0 eq.) and DIPEA (1.16 mL, 6.75 mmol, 3.0 eq.) in DCM (30 mL), benzyl chloroformate (0.43 mL, 2.92 mmol, 1.3 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the solution was stirred at r.t. for 3 hours. The reaction was quenched with 1M aq. citric acid soln. (25 mL). The layers were separated. The aq. phase was extracted with DCM (3×50 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was purified by flash master (column: 50 g, flow: 40 mL/min, Heptane+10% EtOAc to Heptane+50% EtOAc) to yield the title compound.

Workup

  1. additionUpon completion of the addition
  2. customthe cooling bath was removed
  3. customThe reaction was quenched with 1M aq. citric acid soln
  4. customThe layers were separated
  5. extractionThe aq. phase was extracted with DCM (3×50 mL)
  6. dry with materialphases were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash master (column: 50 g, flow: 40 mL/min, Heptane+10% EtOAc to Heptane+50% EtOAc)

Sources & evidence

ORD record
ord-9930c615dd01481884e9b1353c77f8c8
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

Loading…