Acetic Acid → 9-(3,4-Dichloro-phenylamino)-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester

HRID 554476Notes

Reaction equation

HRID 554476 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[Cl:9])[NH2:5].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][C:38]2([CH2:45][CH2:44][C:43](=O)[CH2:42][CH2:41]2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>ClCCCl>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][C:38]2([CH2:45][CH2:44][CH:43]([NH:5][C:4]3[CH:6]=[CH:7][C:8]([Cl:9])=[C:2]([Cl:1])[CH:3]=3)[CH2:42][CH2:41]2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 72573,4-DichloroanilineHCID 5049666Sodium triacetoxyborohydride2×HCID 51072194tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 674592189-(3,4-Dichloro-phenylamino)-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

3,4-Dichloroaniline (364 mg, 2.2 mmol), sodium triacetoxyborohydride (889 mg, 4.20 mmol) and acetic acid (0.24 mL, 4.20 mmol) were added to a solution of 9-oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (561 mg, 2.10 mmol) in 1,2-dichloroethane (30 mL) with crunched 4A mol sieves (10 g). The mixture was stirred a room temperature over night. Additional 4A mol sieves (12 g) and sodium triacetoxyborohydride (445 mg) was added and the mixture was stirred over night. The reaction was quenched with water and 5% citric acid was added. The mixture was filtered through kieselguhr and the filtrated was evaporated until only the aqueous layer remained. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic phases were washed with brine, dried with sodium sulphate, filtered and evaporated to give the crude product. Flash chromatography (ethyl acetale/heptane) gave 9-(3,4-dichloro-phenylamino)-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (258 mg, 0.624 mmol, 30%).

Workup

  1. stirringthe mixture was stirred over night
  2. customThe reaction was quenched with water and 5% citric acid
  3. additionwas added
  4. filtrationThe mixture was filtered through kieselguhr
  5. customthe filtrated was evaporated until only the aqueous layer
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried with sodium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customto give the crude product

Sources & evidence

ORD record
ord-7c95454c58b8494da1dadab1be3a1192
Source dataset
uspto-grants-2011_11
Patent number
US08049012B2

Reaction notes

Loading…