N,N,N',N'-Tetramethylethylenediamine → HCID 178517620, compound

HRID 239011Notes

Reaction equation

HRID 239011 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[CH:9]2)=[CH:4][CH:3]=1.C(=O)=[O:13].C(O)(C)C.[Li]CCCC.CN(CCN(C)C)C>C1COCC1>[C:9]1([OH:13])[C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 122574417-BromoisoquinolineHCID 86586944Isopropanol carbon dioxideHCID 178418339Butyllithium

Product 1

HCID 178517620HCID 178517620, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

7-Bromoisoquinoline (40 mg, 0.193 mmol, 3 equiv) was dissolved in THF (1 mL, 0.19 M) and cooled down to −72° C. (dry ice-isopropanol bath), after which n-BuLi (88 μL, 2.3 M, 0.19 mmol, 3 equiv) was added dropwise. After 40 minutes, TMEDA (88 μL, 0.58 mmol, 9 equiv) was added into the solution. After 10 minutes, O-TBS-estrone (25 mg, 0.065 mmol, 1 equiv) in THF (0.3 mL, 0.22 M in THF) was added dropwise into the reaction solution. After 40 minutes, the reaction was quenched by the addition of sat. aq. NaHCO3 (5 mL). The aqueous layer was extracted four times (4×10 mL) with EtOAc, washed with sat. aq. NaCl (20 mL), dried over MgSO4, filtered, and concentrated in vacuo. Flash column chromatography (silica gel, 30% EtOAc:hexanes) afforded isoquinolinol Compound 28 (25 mg, 74%) as a yellow foam: Rf=0.31 (1:1 EtOAc:DCM); [α]D=+16.9° (c 0.54, CH2Cl2); IR (neat) νmax=3210, 1496, 1285, 1251, 837 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.28 (s, 1H), 8.51 (d, J=4.8 Hz, 1H), 7.88 (d, J=7.8 Hz, 2H), 7.79 (d, J=8.9 Hz, 1H), 7.65 (d, J=5.6 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 6.55-6.50 (m, 2H), 2.87-2.73 (m, 2H), 2.59 (ddd, J=5.1, 9.8, 14.8 Hz, 1H), 2.25 (ddd, J=4.4, 12.5, 17.1 Hz, 1H), 2.10-2.00 (m, 2H), 1.96-1.91 (m, 1H), 1.79 (td, J=4.0, 11.2 Hz, 1H), 1.75-1.65 (m, 2H), 1.50 (dddd, J=2.2, 10.8, 12.7, 21.6 Hz, 1H), 1.47-1.32 (m, 1H), 1.33-1.22 (m, 2H), 1.15 (s, 3H), 0.95 (s, 9H), 0.57 (td, J=4.1, 12.8 Hz, 1H), 0.16 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 153.2, 152.8, 145.2, 142.9, 137.6, 134.6, 132.8, 130.8, 127.9, 125.9, 125.3, 125.2, 120.0, 119.8, 117.0, 86.1, 48.3, 47.4, 43.3, 39.5, 38.9, 33.7, 29.6, 27.4, 26.1, 25.7, 24.2, 18.1, 14.8; HRMS (ESI-TOF) calcd for C33H43NO2Si [M+H]+: 514.3136; found: 514.3140.

Workup

  1. waitAfter 10 minutes
  2. waitAfter 40 minutes
  3. customthe reaction was quenched by the addition of sat. aq. NaHCO3 (5 mL)
  4. extractionThe aqueous layer was extracted four times (4×10 mL) with EtOAc
  5. washwashed with sat. aq. NaCl (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e7a59ad2ea27462a807e565353f9bc98
Source dataset
uspto-grants-2014_02
Patent number
US08642766B2

Reaction notes

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