Acetic Acid → HCID 58763951, compound

HRID 859191Notes

Reaction equation

HRID 859191 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([NH2:11])=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[N:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[N:7]=1)=[O:5])[CH3:2].[C:26]([O:30][C:31](=[O:36])[NH:32][CH2:33][CH:34]=O)([CH3:29])([CH3:28])[CH3:27].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH2:1]([O:3][C:4]([C:6]1[C:10]([NH:11][CH2:34][CH2:33][NH:32][C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:36])=[C:9]([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[N:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 4247255tert-butyl N-(2-oxoethyl)carbamate2×HCID 5049666Sodium triacetoxyborohydride2×HCID 58747008HCID 58747008, compound

Product 1

HCID 58763951HCID 58763951, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-amino-1-(2-chlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (I-4a, 1.88 g, 5 mmol) and (2-oxo-ethyl)-carbamic acid tert-butyl ester (1590 mg, 10 mmol) in 1,2-dichloroethane (60 ml) at room temperature was added glacial acetic acid (858 microliters, 15 mmol) and NaBH(OAc)3 (2540 mg, 12 mmol). The reaction mixture was stirred for 23 hours, then additional (2-oxo-ethyl)-carbamic acid tert-butyl ester (500 mg, 3.14 mmol) and NaBH(OAc)3 (1000 mg, 4.7 mmol) were added. The reaction mixture was stirred for an additional 24 hours, quenched with 1 N NaOH, and diluted with CH2Cl2. The organic layer was separated and the aqueous layer extracted with CH2Cl2. The combined organic phases were washed with 0.5 M aqueous citric acid, 1 N NaOH, and saturated aqueous NaCl, dried, and concentrated in vacuo. The crude residue was purified on a Biotage 40+M column using CH2Cl2/MeOH (100:1) to give the desired product I-4b (900 mg): +ES MS (M+1) 519.5.

Workup

  1. stirringThe reaction mixture was stirred for an additional 24 hours
  2. customquenched with 1 N NaOH
  3. additiondiluted with CH2Cl2
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with CH2Cl2
  6. washThe combined organic phases were washed with 0.5 M aqueous citric acid, 1 N NaOH, and saturated aqueous NaCl
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified on a Biotage 40+M column

Sources & evidence

ORD record
ord-80f69b5954ad421e95891ac53f4d7f40
Source dataset
uspto-grants-2006_12
Patent number
US07151097B2

Reaction notes

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