Acetic Acid → 2-{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenyl}-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

HRID 1027414Notes

Reaction equation

HRID 1027414 reaction equation
[C:1]([Si:5]([CH3:22])([CH3:21])[O:6][CH:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[C:15]([F:20])[CH:14]=2)[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26]([C:28]1([CH2:41][CH:42]=O)[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1)=O)C.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:37]([O:36][C:34]([N:31]1[CH2:32][CH2:33][C:28]2([C:26](=[O:25])[N:19]([C:16]3[CH:17]=[CH:18][C:13]([CH:10]4[CH2:11][CH2:12][CH:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:22])[CH3:21])[CH2:8][CH2:9]4)=[CH:14][C:15]=3[F:20])[CH2:42][CH2:41]2)[CH2:29][CH2:30]1)=[O:35])([CH3:38])([CH3:39])[CH3:40]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 584784234-(2-Oxoethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl esterHCID 674792044-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenylamine

Product 1

HCID 674789912-{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenyl}-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenylamine (520 mg, 1.7 mmol, 1 equiv) was dissolved in DCE (15 mL). To this solution was transferred a solution of 4-(2-oxo-ethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (598 mg, 2.07 mmol, 1 equiv.) in DCE (5 mL). To this clear solution was then added acetic acid (372 mg, 6.21 mmol, 3 equiv) in DCM (2 mL), followed by addition of powder NaBH(OAc)3 (1.31 g, 6.2 mmol, 3 equiv.) in one portion under N2 at rt. The yellowish milky solution was stirred at rt overnight. The reaction was diluted with DCM (10 mL) and quenched with 10 mL of aqueous NaHCO3. The two layers were separated, and the aqueous layer was extracted with DCM (10 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), brine (15 mL), dried (anhydrous potassium carbonate), filtered, and concentrated to obtain the title compound as a liquid and was used in next step without further purification.

Workup

  1. customquenched with 10 mL of aqueous NaHCO3
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with DCM (10 mL×2)
  4. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), brine (15 mL)
  5. dry with materialdried (anhydrous potassium carbonate)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4f9c64ec29994463b64663856c7defe2
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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