4-Methylmorpholine → HCID 57816420, compound

HRID 1751403Notes

Reaction equation

HRID 1751403 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]([OH:22])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[NH2:48][CH:49]1[C:58](=[O:59])[C:57]2[C:52](=[CH:53][C:54]([Br:60])=[CH:55][CH:56]=2)[O:51][CH2:50]1.C(=O)(O)[O-].[Na+].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.O>[Br:60][C:54]1[CH:53]=[C:52]2[C:57]([C:58](=[O:59])[CH:49]([NH:48][C:20]([C@@H:16]3[CH2:17][CH2:18][CH2:19][N:15]3[C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])=[O:22])[CH2:50][O:51]2)=[CH:56][CH:55]=1

Participants

10

Reactant 6

HCID 79724-Methylmorpholine2×HCID 25517Ammonium ChlorideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67265863HCID 67265863, compound

Product 1

HCID 57816420HCID 57816420, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

N-Methylmorpholine (2.14 mL, 19.4 mmol) was added to a mixture of (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (1.93 g, 8.98 mmol) and 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (3.41 g, 8.98 mmol), in N,N-dimethylformamide (6 mL). After 5 min solution of 3-amino-7-bromochroman-4-one hydrochloride (2.5 g, 8.9 mmol) and N-methylmorpholine (2.14 mL, 19.4 mmol) in N,N-dimethylformamide (6 mL) was added. After 1 hour the mixture was diluted with ethyl acetate (100 mL) and was with water (2×25 mL), saturated sodium bicarbonate (25 mL), saturated ammonium chloride (25 mL) and dried over sodium sulfate. The mixture was filtered and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluant of (10% methanol in ethylacetate) and hexane. The product containing fractions were combined and the solvent was removed under reduced pressure to provide (2S)-tert-butyl 2-(7-bromo-4-oxochroman-3-ylcarbamoyl)pyrrolidine-1-carboxylate (3.23 g, 7.35 mmol, 84%).

Workup

  1. dry with materialdried over sodium sulfate
  2. filtrationThe mixture was filtered
  3. customthe solvent was removed under reduced pressure
  4. additionThe product containing fractions
  5. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-eb110f0a89f04b7aa095c1e01ab2b200
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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