2,6-Lutidine → HCID 54141002, compound

HRID 1635680Notes

Reaction equation

HRID 1635680 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:14]=[CH:13]2)[CH2:9][CH2:10]O)[CH:5]=[CH:6][CH:7]=1.[N:29]1C(C)=CC=[CH:31][C:30]=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Li]CC#N>ClCCl.O1CCCC1>[CH2:22]([O:21][C:19]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:20]=1[N:12]([C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)[CH2:9][CH2:10][CH2:31][C:30]#[N:29])[CH:13]=[CH:14]2)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 53971920HCID 53971920, compoundHCID 178506876HCID 178506876, compound

Product 1

HCID 54141002HCID 54141002, compoundYield 78.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (3R)-(−)-3-(3-bromophenyl)-3-(7-benzyloxyindol-1-yl)propan-1-ol (5.10 g, 11.62 mmol) and 2,6-lutidine (1.24 g, 11.62 mmol) in dry dichloromethane (20.0 ml) was added dropwise to a magnetically stirred solution of trifluoromethanesulfonic anhydride (2.20 ml, 13.10 mmol) in dichloromethane (40.0 ml) at −10° C. under nitrogen over a 25 min. period. The resulting grey solution was stirred below −10° C. for 20 min., quenched with water (250 ml), extracted into dichloromethane (2×200 ml), the combined organic extracts were washed with water (200 ml), dried (Na2SO4) and the solvent removed in vacuo at room temperature to give an orange/brown oil which was dissolved in dry tetrahydrofuran (40.0 ml) and added dropwise to the stirred lithio acetonitrile reagent(52.19 mmol) in tetrahydrofuran at −70° C. TLC inspection immediately after the addition showed that the reaction was complete. Quenched with water (20.0 ml), diluted with ethyl acetate (300 ml), washed with brine (2×200 ml), dried (Na2SO4) and adsorbed onto silica (ca. 12.0 g). Column chromatography (ethyl acetate-light petroleum (b.p. 40-60° C.), 1:4) gave the title compound as a pale yellow oil (4.17 g, 78%). (Found: C, 67.62; H, 5.04; N, 5.94; Br, 17.60. C26H23BrN2O requires C, 67.98; H, 5.05; N, 6.10; Br, 17.39%); [α]D19 −138 (c=0.010 gml−1 , CHCl3); νmax (thin film)/cm−1 3064, 2934, 2871, 2246.5 (CN), 1575; δH (270 MHz) 1.55 (2H, m, 2×butyl 3-H); 2.23 (2H, t, 2×butyl 4-H, 3J4,3=6.9 Hz); 2.30 (2H, m, 2×butyl 2-H); 5.17 (2H, q, CH2Ph, 2J=10.9 Hz); 6.35 (1H, dd, butyl 1-H, 3J1,2=9.7, 3J1,2=5.8 Hz); 6.56 (1H, d, 3-H, 3J2,2=3.3 Hz); 6.74 (1H, d, 6-H, Jo=7.9 Hz); 6.95 (1H, d, 4-H, Jo=7.9 Hz); 7.00 (1H, t, 5-H, Jo=7.9 Hz); 7.08 (1H, t, 5′-H, Jo=7.9 Hz); 7.14 (1H, d, 2-H, 3J3,2=3.3 Hz); 7.21 (1H, d, 6′-H, Jo=8.9 Hz); 7.25 (1H, t, 2′-H, Jm=1.1 Hz); 7.34 (1H, dd, 4′-H, Jo=8.4, Jm=1.5 Hz); 7.42 (5H, m, 5ArH). δC (67.8 MHz) 16.5 (butyl 3-C); 22.3 (butyl 4-C); 34.4 (butyl 2-C); 58.8 (butyl 1-C); 70.6 (PhCH2); 103.5 (indole 3-C); 104.1 (indole 6-C); 114.2 (indole 4-C); 119.1 (CN); 120.2 (indole 5-C); 122.6 (3′-C); 124.5 (indole 2-C); 125.0 (6′-C); 130.7 (1′-C); 136.5 (benzyl ipso-C); 144.2 (indole 7a-C); 147.0 (indole 7-C). The remaining signals lie between 128.2-130.6 ppm and cannot be assigned with any certainty; m/z 460.1, 458.1 (3.43, 3.32), 369.1, 367.1 (1.79, 1.66), 239.0, 237.0 (7.01, 7.72), 171.0, 169.0 (26.03, 26.07), 143.1 (100), 132.1 (6.44), 116.0 (9.37).

Workup

  1. customquenched with water (250 ml)
  2. extractionextracted into dichloromethane (2×200 ml)
  3. washthe combined organic extracts were washed with water (200 ml)
  4. dry with materialdried (Na2SO4)
  5. customthe solvent removed in vacuo at room temperature
  6. customto give an orange/brown oil which
  7. additionTLC inspection immediately after the addition
  8. customQuenched with water (20.0 ml)
  9. additiondiluted with ethyl acetate (300 ml)
  10. washwashed with brine (2×200 ml)
  11. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-56935145fe5044ecad768399513b516c
Source dataset
uspto-grants-2003_01
Patent number
US06509476B1

Reaction notes

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