Hydrochloric Acid → HCID 54670055, compound

HRID 1184419Notes

Reaction equation

HRID 1184419 reaction equation
C([BH3-])#N.[Na+].Cl.[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([NH:21][C:22]([CH:24]2[CH2:29][CH2:28][C:27](=[N+:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH2:26][CH:25]2[C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=[O:23])[C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[CH:9][CH:8]=1.[OH-].[Na+]>CO>[F:6][C:7]1[CH:8]=[CH:9][C:10]([CH:13]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[NH:21][C:22]([CH:24]2[CH2:29][CH2:28][CH:27]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)[CH2:26][CH:25]2[C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=[O:23])=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 86692741HCID 86692741, compound

Product 1

HCID 54670055HCID 54670055, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

A second reaction vessel was charged with MeOH (2 mL), cooled to −78° C. using a dry-ice/acetone cooling bath, and treated with sodium cyanoborohydride (0.105 g, 1.673 mmol), followed by the dropwise addition of HCl (1.339 mL, 1.673 mmol, 1.25 M in MeOH). After stirring at −78° C. for approximately 5 min, the material from Step A was added portion wise over approximately 15 min. The reaction was gradually warmed to rt and aged for 12 h. A solution of aq. 5 M NaOH was added until the pH of the reaction mixture was basic. The biphasic mixture was filtered through a plug of Celite™ while rinsing with EtOAc. The organic layer of the filtrate was separated and washed with saturated aq. NaCl, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography on silica gel via gradient elution with 0-50% EtOH/EtOAc. The purified fractions were combined and concentrated to afford the faster eluting isomer (at * carbon) as Example 3 [HPLC/MS: 509.3 (M+1); Rt=2.85 min] and the slower eluting isomer (at * carbon) as Example 4 [HPLC/MS: 509.3 (M+1); Rt=2.83 min].

Workup

  1. temperatureThe reaction was gradually warmed to rt and aged for 12 h
  2. filtrationThe biphasic mixture was filtered through a plug of Celite™
  3. washwhile rinsing with EtOAc
  4. customThe organic layer of the filtrate was separated
  5. washwashed with saturated aq. NaCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash chromatography on silica gel via gradient elution with 0-50% EtOH/EtOAc
  10. concentrationconcentrated
  11. customto afford the
  12. washfaster eluting isomer (at * carbon) as Example 3 [HPLC/MS: 509.3 (M+1); Rt=2.85 min]
  13. washthe slower eluting isomer (at * carbon) as Example 4 [HPLC/MS: 509.3 (M+1); Rt=2.83 min]

Sources & evidence

ORD record
ord-76140fc5ba42420d961f4684c6a20761
Source dataset
uspto-grants-2014_03
Patent number
US08669252B2

Reaction notes

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