Lithium borohydride → HCID 58827198, compound

HRID 923272Notes

Reaction equation

HRID 923272 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, 1H), 2.78-2.96 (m, 3H), 3.91 (s, 3H), 4.10 (d, J=11.6 Hz, 1H), 4.46 (d, J=11.6 Hz, 1H), 6.57 (d, J=8.3 Hz, 1H), 6.73 (s, 1H), 7.13-7.18 (obs m, 1H), 7.16 (s, 1H), 7.52 (s, 1H).

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-f204e5a016724ffcadb0b23d85875640
Source dataset
uspto-grants-2016_03
Patent number
US09278969B2

Reaction notes

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