Hydrochloric Acid → HCID 178495116, compound

HRID 2065803Notes

Reaction equation

HRID 2065803 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]([CH3:20])([CH3:19])[C:15](OC)=[O:16])=[N:11][C:10]=1[C:21]1[N:26]=[C:25]2[O:27][C:28]([NH:30][C@@H:31]([CH3:36])[CH2:32][CH2:33][O:34][CH3:35])=[N:29][C:24]2=[CH:23][CH:22]=1.[BH4-].[Li+].Cl>C(OCC)C.C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]([CH3:20])([CH3:19])[CH2:15][OH:16])=[N:11][C:10]=1[C:21]1[N:26]=[C:25]2[O:27][C:28]([NH:30][C@@H:31]([CH3:36])[CH2:32][CH2:33][O:34][CH3:35])=[N:29][C:24]2=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 178495118HCID 178495118, compound

Product 1

HCID 178495116HCID 178495116, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 2-[5-(2,4-difluorophenyl)-4-[2-[[(1S)-3-methoxy-1-methyl-propyl]amino]oxazolo[5,4-b]pyridin-5-yl]-1H-imidazol-2-yl]-2-methyl-propanoate (50 g, 100.1 mmol) is dissolved in a mixture of diethyl ether (1 L) and THF (500 mL). The mixture is cooled to 0° C. and lithium borohydride (4.36 g, 200.19 mmol) is added. The reaction mixture is stirred at RT under a nitrogen atmosphere for 2 h. 1 M HCl (600 mL) is slowly added (gas evolution) and the resulting mixture is stirred for 1.5 h at RT. The layers are separated and the aqueous phase is extracted with methyl tert-butyl ether. The aqueous layer is basified (pH=8) by the addition of 2 M NaOH (200 mL) and is extracted with dichloromethane (3×400 mL). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure to a brown foam. The crude is eluted through a silica gel column (eluent: dichloromethane/3N NH3 in methanol 95:5) to obtain the desired product as a violet colored foam (35 g). The solid is suspended in a mixture of 2:1 heptane/methyl tert-butyl ether and sonicated. The suspension is stirred at RT overnight. The solid is filtered and dried under a vacuum to afford the title compound as a crystalline off-white solid (30 g, 64%). MS (m/z): 472 (M+1).

Workup

  1. stirringthe resulting mixture is stirred for 1.5 h at RT
  2. customThe layers are separated
  3. extractionthe aqueous phase is extracted with methyl tert-butyl ether
  4. additionby the addition of 2 M NaOH (200 mL)
  5. extractionis extracted with dichloromethane (3×400 mL)
  6. dry with materialThe combined organic layers are dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to a brown foam
  9. washThe crude is eluted through a silica gel column (eluent: dichloromethane/3N NH3 in methanol 95:5)

Sources & evidence

ORD record
ord-453c54e9c8124ba992e27c5d535ce4e3
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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