Lithium borohydride → HCID 58827198, compound

HRID 1877953Notes

Reaction equation

HRID 1877953 reaction equation
C[O:2][C:3]([C:5]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][C:14]=2[O:21][CH3:22])[N:9]2[CH:10]=[N:11][CH:12]=[C:8]2[CH2:7][CH2:6]1)=O.[BH4-].[Li+]>C1COCC1>[OH:2][CH2:3][C:5]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][C:14]=2[O:21][CH3:22])[N:9]2[CH:10]=[N:11][CH:12]=[C:8]2[CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 588272065-(4-Cyano-2-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester

Product 1

HCID 58827198HCID 58827198, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

5-(4-Cyano-2-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester (0.100 g, 0.336 mmol) is dissolved in THF (3 mL) and cooled to −10° C. A THF solution of lithium borohydride (0.08 mL, 2 M) is then added. The solution is removed from the cold bath and allowed to warm to room temperature before being heated to 40° C. at which time additional lithium borohydride (0.08 mL, 2 M) is added. The solution is maintained at that temperature for 1.5 h before being allowed to cool to room temperature and being quenched by the addition of 1 M HCl. Following aqueous workup the residue is warmed to 80° C. in ethanolamine/CH3CN (1:3) for 1 h. The solution is then concentrated and the residue purified via prep HPLC (reversed phase; 5-100% CH3CN/H2O and 0.1% TFA). Conversion to the free base provided 4-(5-hydroxymethyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-methoxybenzonitrile as a white solid. MS (ESI) m/z 270.1 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.55-2.67 (m, 1 H), 2.78-2.96 (m, 3 H), 3.91 (s, 3 H), 4.10 (d, J=11.6 Hz, 1 H), 4.46 (d, J=11.6 Hz, 1 H), 6.57 (d, J=8.3 Hz, 1 H), 6.73 (s, 1 H), 7.13-7.18 (obs m, 1 H), 7.16 (s, 1 H), 7.52 (s, 1 H).

Workup

  1. customThe solution is removed from the cold bath
  2. temperatureto warm to room temperature
  3. temperaturebefore being heated to 40° C. at which time additional lithium borohydride (0.08 mL, 2 M)
  4. additionis added
  5. temperatureThe solution is maintained at that temperature for 1.5 h
  6. temperatureto cool to room temperature
  7. custombeing quenched by the addition of 1 M HCl
  8. temperatureFollowing aqueous workup the residue is warmed to 80° C. in ethanolamine/CH3CN (1:3) for 1 h
  9. concentrationThe solution is then concentrated
  10. customthe residue purified via prep HPLC (reversed phase; 5-100% CH3CN/H2O and 0.1% TFA)

Sources & evidence

ORD record
ord-185447965d0546248b94e959ac7394f7
Source dataset
uspto-grants-2012_11
Patent number
US08314097B2

Reaction notes

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