Acetic Acid → tert-butyl 2-(3-(5-(2-methoxyphenethoxy)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzylamino)ethyl(methyl)carbamate

HRID 2196559Notes

Reaction equation

HRID 2196559 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][CH:26]=[CH:25][C:4]=1[CH2:5][CH2:6][O:7][C:8]1[N:12]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[C:16]#[N:17])[N:11]=[C:10]([C:21]([F:24])([F:23])[F:22])[CH:9]=1.[CH3:29][N:30]([CH2:38][CH:39]=O)[C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].C(O)(=O)C.C([BH3-])#N.[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][CH:26]=[CH:25][C:4]=1[CH2:5][CH2:6][O:7][C:8]1[N:12]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH2:16][NH:17][CH2:39][CH2:38][N:30]([CH3:29])[C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[N:11]=[C:10]([C:21]([F:23])([F:24])[F:22])[CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 10725881tert-butyl N-methyl-N-(2-oxoethyl)carbamateHCID 693009123-(5-(2-methoxyphenethoxy)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzonitrile

Product 1

HCID 69094739tert-butyl 2-(3-(5-(2-methoxyphenethoxy)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzylamino)ethyl(methyl)carbamateYield 24.34%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 131 (85 mg, 0.219 mmol) in THF (0.4 mL) at 0° C. under nitrogen was added BH3 in THF (1.114 mL, 1.0M solution, 1.114 mmol). The reaction was stirred at room temperature for 1 hour then it was cooled to at 0° C. and quenched carefully with methanol. The mixture was concentrated, MeOH (1.5 mL), tert-butyl methyl(2-oxoethyl)carbamate (38.0 mg, 0.219 mmol) and acetic acid (25.1 μL, 0.439 mmol) were added and the mixture was stirred at room temperature for 1 h after which sodium cyanoborohydride (34.5 mg, 0.549 mmol) was added. After 16 h, the reaction was worked-up as usual and the residue was purified by silica gel chromatography (Biotage 12M, 0-5% MeOH/DCM) to give 132 (29.3 mg, 0.053 mmol, 24.34% yield) as clear oil. LRMS(ESI): (calc.) 548.6 (found) 549.2 (MH)+.

Workup

  1. temperatureit was cooled to at 0° C.
  2. customquenched carefully with methanol
  3. concentrationThe mixture was concentrated
  4. additionwas added
  5. waitAfter 16 h
  6. customwas purified by silica gel chromatography (Biotage 12M, 0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-6b6928531f6449ee8a28dc734ec20d77
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

Loading…