Hydrochloric Acid → HCID 86604618, compound

HRID 2373920Notes

Reaction equation

HRID 2373920 reaction equation
CC1(C)CCCC(C)(C)N1.[CH2:11]([O:18][C:19]1[CH:20]=[C:21]([CH:27]([C:29]2[C:34]([Cl:35])=[N:33][CH:32]=[CH:31][N:30]=2)[OH:28])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Li]CCCC.ClC1C=NC=CN=1.C(OC1C=C(C=CC=1OC)C=O)C1C=CC=CC=1.Cl>C1COCC1>[CH2:11]([O:18][C:19]1[CH:20]=[C:21]([CH:27]([C:29]2[C:34]([Cl:35])=[N:33][CH:32]=[CH:31][N:30]=2)[OH:28])[CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 73277ChloropyrazineHCID 806713-Benzyloxy-4-methoxybenzaldehydeHCID 86604617HCID 86604617, compoundHCID 178418339Butyllithium

Product 1

HCID 86604618HCID 86604618, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(3-Benzyloxy-4-methoxyphenyl)-(3-chloropyrazin-2-yl)-methanol 2,2,6,6-Tetramethylpiperidine (1775 μl, 1.2 eq.) was added dropwise over 5 min into the THF (20 ml) solution of n-BuLi (2.5 M in cyclohexane, 4.2 ml, 1.2 eq.), which was cooled in a dry ice/acetone bath. The reaction vessel was removed from the cooling bath and allowed to warm to 0° C. for 15 min, then cooled back to −78° C. and charged with chloropyrazine (780 μl, 8.733 mmol) dropwise over 5 min. The reaction was allowed to react for 15 min, and charged with a THF (10 ml) solution of 3-benzyloxy-4-methoxybenzaldehyde (2328 mg, 1.1 eq.) over 10 min. After 2 h, the reaction mixture was warmed to rt and aqueous HCl (1 N, 15 ml) was added. The mixture was extracted with CH2Cl2 (3×50 ml). The combined extracts were washed with water (50 ml) and brine (50 ml), and dried over MgSO4. After concentration in vacuo, a crude black oil (3.163 g) was obtained that was then purified by chromatography on silica gel (500 ml 10%, 30%, 40%, 50%, and 60% EtOAc/Hexane) and a brown oil of (3-benzyloxy-4-methoxyphenyl)-(3-chloropyrazin-2-yl)-methanol was obtained; 1H NMR (DMSO-d6, 400 MHz) δ 3.74 (s, 3H), 5.04 (s, 2H), 6.00 (d, 1H, J=6.0 Hz), 6.09 (d, 1H, J=6.0 Hz), 7.10 (s, 1H), 7.31-7.42 (m, 7H), 8.43 (d, 1H, J=2.4 Hz), 8.67 (d, 1H, J=2.4 Hz); MS (ES): 357.4/359.4 (M/M+2).

Workup

  1. temperaturewas cooled in a dry ice/acetone bath
  2. customThe reaction vessel was removed from the cooling bath
  3. temperaturecooled back to −78° C.
  4. customto react for 15 min
  5. temperaturethe reaction mixture was warmed to rt
  6. extractionThe mixture was extracted with CH2Cl2 (3×50 ml)
  7. washThe combined extracts were washed with water (50 ml) and brine (50 ml)
  8. dry with materialdried over MgSO4
  9. concentrationAfter concentration in vacuo
  10. customa crude black oil (3.163 g) was obtained
  11. customthat was then purified by chromatography on silica gel (500 ml 10%, 30%, 40%, 50%, and 60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-91398f41f94b4af0a6265f087cc1c7b1
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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