Water → 6-Benzyloxy-2-(3-hydroxybenzyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline

HRID 1944190Notes

Reaction equation

HRID 1944190 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[CH2:15][N:14]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][Si](C(C)C)(C(C)C)C(C)C)[CH:23]=1)[CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1.O.CCOC(C)=O>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[CH2:15][N:14]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=1)[CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 11078149TBAF tetrahydrofuranHCID 25071536HCID 25071536, compound

Product 1

HCID 250724816-Benzyloxy-2-(3-hydroxybenzyl)-7-methoxy-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(benzyloxy)-7-methoxy-2-(3-(triisopropylsilyloxy)benzyl)-1,2,3,4-tetrahydroisoquinoline (2.7 g, 5 mmol) in THF (50 mL) was cooled to 0° C. and 1M TBAF/THF (5.5 mL, 5.5 mmol) added drop wise. The solution was stirred at 0 C. for 1 h 30 min and water (20 mL) added as well as EtOAc (80 mL). The organic layer was washed with water, brine, dried with MgSO4, filtered and concentrated under reduced pressure. The resulting solid was washed with hexane, filtered and dried. 1.7 g (90%), white powder, mp=78-79° C.; Rf: 0.12 (Hexane/EtOAc 3:1), 1H NMR (270 MHz, CDCl3) δ 2.63-2.78 (4H, m, 2×CH2), 3.52 (2H, s, CH2), 3.58 (2H, s, CH2), 3.79 (3H, s, CH3O), 5.08 (2H, s, OCH2), 6.48 (1H, s, ArH), 6.60 (1H, s, ArH), 6.68 (1H, dd, J 8.2 and 2.5 Hz, ArH), 6.82 (1H, d, J 2.5 Hz, ArH), 6.88 (1H, d, J 7.7 Hz, ArH), 7.15 (1H, dd, J 8.2 and 7.7 Hz, 1H, ArH), 7.26-7.47 (5H, m, ArH). 13C NMR (67.5 MHz, CDCl3) δ 12.7((CH3)2CHSi), 18.0 ((CH3)2CHSi), 28.8 (CH2), 50.7 (CH2), 55.9 (CH2), 56.1 (CH3O), 62.7 (CH2), 71.2 (OCH2), 110.1 (CH(Ar)), 114.3 (CH(Ar)), 118.6 (CH(Ar)), 120.8 (CH(Ar)), 126.4 (C(Ar)), 127.4 (CH(Ar)), 127.6 (C(Ar)), 127.8 CH(Ar)), 128.6 (CH(Ar)), 129.2 (CH(Ar)), 137.4 (C(Ar)), 140.0 (C(Ar)), 146.6 (C(Ar)), 147.9 (C(Ar)) and 156.1 (C(Ar)). LC/MS (APCI+) tr=5.12 min m/z 376.59 (M++H); MeOH/H2O 50/50 to 95/5 (5 min); HPLC tr=3.26 min (100%). (CH3CN/H2O 90/10)

Workup

  1. washThe organic layer was washed with water, brine
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. washThe resulting solid was washed with hexane
  6. filtrationfiltered
  7. customdried
  8. customLC/MS (APCI+) tr=5.12 min m/z 376.59 (M++H)
  9. customto 95/5 (5 min)
  10. custom=3.26 min (100%)

Sources & evidence

ORD record
ord-17346b6674a6403982b1bc64eb714d7d
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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