Sodium Hydroxide → HCID 86607897, compound

HRID 736797Notes

Reaction equation

HRID 736797 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C@@H:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][C@:20]2([CH3:36])[C:32](OC)=[O:33])(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[C:67]([O:71][NH2:72])([CH3:70])([CH3:69])[CH3:68]>[Cl-].[Na+].O.CN(C=O)C.C(N(CC)CC)C.CO.C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C@@H:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[CH2:21][C@@:20]2([C:32](=[O:33])[NH:72][O:71][C:67]([CH3:70])([CH3:69])[CH3:68])[CH3:36])(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2777906O-tert-butylhydroxylamine hydrochlorideHCID 68817252HCID 68817252, compound

Product 1

HCID 86607897HCID 86607897, compoundYield 93.3%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of (3S,4R)-1-tert-butyl 3-methyl 4-(4-(benzyloxy)phenylsulfonamido)-3-methylpiperidine-1,3-dicarboxylate (4.494 g, 8.67 mmol), 5 M NaOH (10 mL), and THF (20 mL) was added methanol until the reaction became homogeneous. The solution was stirred at 45° C. overnight, then diluted with pH 4 NaH2PO4 (aq) and extracted with ethyl acetate (3×). Combined organic extracts were dried over Na2SO4 and concentrated to give an orange solid. The solid was then combined with benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (4.766 g, 10.78 mmol), O-tert-butylhydroxylamine hydrochloride (2.442 g, 19.28 mmol), triethylamine (5.4 mL), and DMF (10 mL) and the reaction mixture was stirred overnight at room temperature. The mixture was then diluted with brine and extracted with ethyl acetate (3×). The combined organic extracts were dried over Na2SO4 and purified via column chromatography on silica gel eluting with 30% ethyl acetate/hexanes to give (3S,4R)-tert-butyl 4-(4-(benzyloxy)phenylsulfonamido)-3-(tert-butoxycarbamoyl)-3-methylpiperidine-1-carboxylate (4.659 g, 8.09 mmol, 93%) as a colorless solid. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.09 (s, 3H) 1.23-1.25 (m, 9H) 1.40-1.51 (m, 10H) 1.57-1.60 (m, 3H) 1.65-1.72 (m, 1H) 2.49 (d, J=15.16 Hz, 1H) 2.72-2.83 (m, 1H) 3.16 (ddd, J=12.38, 8.72, 3.92 Hz, 1H) 3.98 (dt, J=13.58, 2.31 Hz, 1H) 4.31 (d, J=14.65 Hz, 1H) 5.11 (s, 2H) 7.01 (ddd, J=9.41, 2.78, 2.46 Hz, 2H) 7.33-7.44 (m, 5H) 7.78-7.82 (m, 2H).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. dry with materialCombined organic extracts were dried over Na2SO4
  3. concentrationconcentrated
  4. customto give an orange solid
  5. stirringthe reaction mixture was stirred overnight at room temperature
  6. extractionextracted with ethyl acetate (3×)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. custompurified via column chromatography on silica gel eluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-bbc723c1ed7d46008bef84b0379aa480
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

Loading…