Triethylamine → (2R,5R)-5-[(1S,2S)-2-(Cyclopentanecarbonylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20482

Reaction equation

HRID 20482 reaction equation
[CH:1]1([C:6]([OH:8])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:32]([O:36][C:37]([N:39]1[C@@H:44]([C@@H:45]([OH:57])[C@@H:46]([NH2:56])[CH2:47][C:48]2[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=2)[CH2:43][O:42][C@@H:41]([O:58][CH2:59][C:60]([CH3:63])([CH3:62])[CH3:61])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(N(CC)CC)C>ClCCl>[C:32]([O:36][C:37]([N:39]1[C@@H:44]([C@@H:45]([OH:57])[C@@H:46]([NH:56][C:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[O:8])[CH2:47][C:48]2[CH:49]=[C:50]([F:55])[CH:51]=[C:52]([F:54])[CH:53]=2)[CH2:43][O:42][C@@H:41]([O:58][CH2:59][C:60]([CH3:63])([CH3:62])[CH3:61])[CH2:40]1)=[O:38])([CH3:33])([CH3:35])[CH3:34]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 18840Cyclopentanecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68560376(2R,5R)-5-[(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68561969(2R,5R)-5-[(1S,2S)-2-(Cyclopentanecarbonylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl esterYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Stir cyclopentanecarboxylic acid (0.01 mL, 0.12 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (0.02 g, 0.12 mmol) and 1-hydroxybenzotriazole monohydrate (HOBT) (0.02 g, 0.12 mmol) in dichloromethane (1 mL) at room temperature for 30 minutes. Add (2R,5R)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester (0.05 g, 0.11 mmol) in dichloromethane (1 mL) and triethylamine (0.06 mL, 0.44 mmol) and stir at room temperature overnight. Wash with saturated aqueous sodium bicarbonate, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 80:20 hexane:ethyl acetate), to give the desired compound as white solid (0.06 g, 98%).

Workup

  1. washWash with saturated aqueous sodium bicarbonate
  2. dry with materialdry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 80:20 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-3bd97f8c08bd461d95b0c12b8c50c45e
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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