Triethylamine hydrochloride → HCID 86607893, compound

HRID 736792Notes

Reaction equation

HRID 736792 reaction equation
[OH:1][C@@:2]1([C:38](OC)=[O:39])[C@H:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=[C:22]([CH3:30])[CH:21]=3)=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:3]1.[OH-].[Na+].Cl.C(N(CC)CC)C.C(N(C(C)C)CC)(C)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.Cl.[C:89]([O:93][NH2:94])([CH3:92])([CH3:91])[CH3:90]>C(OCC)(=O)C.O.C1COCC1.CO>[C:89]([O:93][NH:94][C:38]([C@:2]1([OH:1])[C@H:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=[C:22]([CH3:30])[CH:21]=3)=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]([C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])[CH2:3]1)=[O:39])([CH3:92])([CH3:91])[CH3:90]

Participants

11

Reactant 6

HCID 11130Triethylamine hydrochlorideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2777906O-tert-butylhydroxylamine hydrochlorideHCID 86607891HCID 86607891, compound

Product 1

HCID 86607893HCID 86607893, compoundYield 42.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-tert-butyl 3-methyl (3R,4R)-3-hydroxy-4-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]piperidine-1,3-dicarboxylate (1.59 g, 2.72 mmol), methanol (10 mL), THF (10 mL) and 1N sodium hydroxide (10.9 mL, 4 eq) was stirred overnight. Triethylamine hydrochloride (2.25 g, 16.32 mmol, 6 eq) was added and the resulting mixture was stirred for awhile and then concentrated in vacuo. The residue was dried by azeotropic evaporation with toluene and then dried under high vacuum for 5 h. This crude carboxylic acid was dissolved in DMF (30 mL) and diisopropylethylamine (1.9 mL, 10.88 mmol, 4.0 eq), BOP reagent (1.56 g, 3.54 mmol, 1.3 eq) and O-tert-butylhydroxylamine hydrochloride (512 mg, 4.08 mmol, 1.5 eq) were added. The reaction was stirred overnight, and then diluted with ethyl acetate and water. The organic phase was washed with water three times. The aqueous layer was re-extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography with 65-70% ethyl acetate/hexane to yield 740 mg (42% in two steps) of tert-butyl (3R,4R)-3-[(tert-butoxyamino)carbonyl]-3-hydroxy-4-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]piperidine-1-carboxylate as white solid. MS: (M+H)+=643.1.

Workup

  1. stirringthe resulting mixture was stirred for awhile and
  2. concentrationthen concentrated in vacuo
  3. dry with materialThe residue was dried by azeotropic evaporation with toluene
  4. customdried under high vacuum for 5 h
  5. dissolutionThis crude carboxylic acid was dissolved in DMF (30 mL)
  6. stirringThe reaction was stirred overnight
  7. washThe organic phase was washed with water three times
  8. extractionThe aqueous layer was re-extracted with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography with 65-70% ethyl acetate/hexane

Sources & evidence

ORD record
ord-399405b3654a4b158369a9db7de49295
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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