Methanol → HCID 68044435, compound

HRID 1524373Notes

Reaction equation

HRID 1524373 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20]([NH:22][CH2:23][CH2:24][C:25]([F:48])([F:47])[CH2:26][C@@H:27]([C:42](OCC)=[O:43])[N:28]([S:32]([C:35]1[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=1)(=[O:34])=[O:33])[CH:29]([CH3:31])[CH3:30])=[O:21])[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[BH4-].[Li+].CO.O>C1COCC1>[NH2:41][C:38]1[CH:37]=[CH:36][C:35]([S:32]([N:28]([CH:29]([CH3:31])[CH3:30])[C@H:27]([CH2:42][OH:43])[CH2:26][C:25]([F:48])([F:47])[CH2:24][CH2:23][NH:22][C:20](=[O:21])[C@H:6]([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:5][C:3]([O:2][CH3:1])=[O:4])(=[O:33])=[O:34])=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 4148881Lithium borohydride2×HCID 86708077HCID 86708077, compound

Product 1

HCID 68044435HCID 68044435, compoundYield 55.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the material from Step 11 (50 mg, 0.073 mmol) in THF (726 μL) at 0° C. were added a solution of 2 M lithium borohydride in THF (145 μL, 0.290 mmol) and methanol (11.75 μL, 0.290 mmol). The reaction mixture was stirred at room temperature for 2 hours. TLC showed not complete reaction. Additional 2 equiv of lithium borohydride was added, stirred at room temperature for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with brine, dried with MgSO4 and concentrated under vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate-hexanes (0:100 to 100:0) to afford 26 mg of the title compound as a colorless foam. LCMS (M+1)=647. 1H NMR (Acetone-d6): δ 7.62 (d, J=8.32 Hz, 2H), 7.46-7.36 (m, 4H), 7.34-7.25 (m, 4H), 7.23-7.15 (m, 3H), 6.76 (d, J=8.32 Hz, 2H), 6.40 (d, J=9.02 Hz, 1H), 5.49 (s, 2H), 4.97 (t, J=10.09 Hz, 1H), 4.42 (d, J=11.05 Hz, 1H), 3.93-3.81 (m, 2H), 3.80-3.69 (m, 2H), 3.66-3.59 (m, 1H), 3.50 (s, 3H), 3.34-3.14 (m, 1H), 3.12-2.95 (m, 1H), 2.46-2.29 (m, 2H), 1.81-1.44 (m, 2H), 1.20 (d, J=8.20 Hz, 6).

Workup

  1. customcomplete reaction
  2. stirringstirred at room temperature for 3 hours
  3. extractionextracted with ethyl acetate (2×15 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-66f95247f9a24b9a8d79ee870ad4d543
Source dataset
uspto-grants-2015_07
Patent number
US09079834B2

Reaction notes

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