Sodium triacetoxyborohydride → (S)-tert-butyl 1-(3-fluoro-4-((3,3,4-trimethylpiperazin-1-yl)methyl)phenyl)ethylcarbamate

HRID 57393Notes

Reaction equation

HRID 57393 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[CH:6][C:7]=1[CH:8]=O.Cl.Cl.[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][C:24]1([CH3:30])[CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO.C(Cl)Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@@H:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[CH:6][C:7]=1[CH2:8][N:26]1[CH2:27][CH2:28][N:23]([CH3:22])[C:24]([CH3:30])([CH3:29])[CH2:25]1

Participants

6

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 232893821,2,2-Trimethylpiperazine dihydrochlorideHCID 86730149(S)-tert-butyl 1-(3-fluoro-4-formylphenyl)ethylcarbamate

Product 1

HCID 86730151(S)-tert-butyl 1-(3-fluoro-4-((3,3,4-trimethylpiperazin-1-yl)methyl)phenyl)ethylcarbamateYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-tert-butyl 1-(3-fluoro-4-formylphenyl)ethylcarbamate (267 mg, 1 mmol) and 1,2,2-trimethylpiperazine dihydrochloride (402 mg, 2 mmol) in THF (5 mL) was stirred at room temperature for 1 h and treated with sodium triacetoxyborohydride (848 mg, 4 mmol). The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with saturated aqueous solution of NaHCO3 (15 mL) and extracted with EtOAc (3×mL). Combined organics were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (MeOH/CH2Cl2 0 to 10%) provided (S)-tert-butyl 1-(3-fluoro-4-((3,3,4-trimethylpiperazin-1-yl)methyl)phenyl)ethylcarbamate as a white solid (186 mg, 49% yield). 1H NMR (400 MHz, CDCl3) δ 7.35 (t, J=7.7 Hz, 1H), 7.03 (dd, J=7.9, 1.9 Hz, 1H), 6.95 (dd, J=11.1, 1.8 Hz, 1H), 4.77 (s, 1H), 3.49 (s, 2H), 2.56 (br s, 4H), 2.24 (br s, 5H), 1.42 (br s, 12H), 1.04 (s, 6H); MS m/z 380.4 (M+H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous solution of NaHCO3 (15 mL)
  2. extractionextracted with EtOAc (3×mL)
  3. dry with materialCombined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ae6e70a6981840ca8057dce146387b84
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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