Triethylamine → HCID 178525103, compound

HRID 2036213Notes

Reaction equation

HRID 2036213 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][C:8]2[O:12][N:11]=[C:10]([OH:13])[CH:9]=2)=[C:4]([CH:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][CH2:18][NH:17]2)[CH:3]=1.CCN(CC)CC.Cl[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>C(Cl)Cl>[CH2:37]([O:36][C:34]([N:17]1[CH2:18][CH2:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]1[C:4]1[CH:3]=[C:2]([Cl:1])[CH:15]=[CH:14][C:5]=1[O:6][CH2:7][C:8]1[O:12][N:11]=[C:10]([OH:13])[CH:9]=1)=[O:35])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 178516275HCID 178516275, compound

Product 1

HCID 178525103HCID 178525103, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of (±)-5-[4-chloro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxymethyl]-isoxazol-3-ol (49 mg, 0.138 mmol, 1.0 eq.) and NEt3 (58 μL, 0.414 mmol, 3.0 eq.) in DCM (3.8 mL), benzyl chloroformate (23 μL, 0.152 mmol, 1.1 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the suspension was stirred at r.t. for 4 hours. The reaction was quenched with 1M aq. citric acid soln. (3.8 mL). The layers were separated. The aq. phase was extracted with DCM (3×). The comb. org. phases were concentrated in vacuo. The residue, redissolved in DMF, was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated (genevac) to give the desired product as a pale yellow solid.

Workup

  1. additionwas added dropwise
  2. additionUpon completion of the addition
  3. customthe cooling bath was removed
  4. customThe reaction was quenched with 1M aq. citric acid soln
  5. customThe layers were separated
  6. extractionThe aq. phase was extracted with DCM (3×)
  7. concentrationphases were concentrated in vacuo
  8. dissolutionThe residue, redissolved in DMF
  9. customwas purified by prep
  10. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated (genevac)

Sources & evidence

ORD record
ord-cac1509ba4434f649614299af2e8dbeb
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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