4-Methylmorpholine → (S)-4-[[(S)-2-(3-Chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-3-hydroxy-butyric acid methyl ester

HRID 2095525Notes

Reaction equation

HRID 2095525 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C@@H:13]([CH3:17])[C:14]([OH:16])=O)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:49][O:50][C:51](=[O:63])[CH2:52][C@H:53]([OH:62])[CH2:54][NH:55][CH2:56][CH:57]([O:60][CH3:61])[O:58][CH3:59].OS([O-])(=O)=O.[K+].CCOC(C)=O>CN(C=O)C>[CH3:49][O:50][C:51](=[O:63])[CH2:52][C@H:53]([OH:62])[CH2:54][N:55]([C:14](=[O:16])[C@@H:13]([NH:12][C:4]1[CH:5]=[CH:6][C:7]([C:8]([F:9])([F:10])[F:11])=[C:2]([Cl:1])[CH:3]=1)[CH3:17])[CH2:56][CH:57]([O:58][CH3:59])[O:60][CH3:61]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66782715(S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionic acid2×HCID 86585043ethylacetate KHSO4HCID 86652695(S)-4-(2,2-Dimethoxy-ethylamino)-3-hydroxy-butyric acid methyl ester

Product 1

HCID 67074923(S)-4-[[(S)-2-(3-Chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-3-hydroxy-butyric acid methyl esterYield 122.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 0.915 g (3.4 mmol) of (S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionic acid (26% ee) (intermediate 32) and 0.394 ml (3.6 mmol) of 4-methylmorpholine in 10.0 ml of DMF, was added at 0° C. 1.86 g (4.9 mmol) of HATU, followed after 30 min by 1.20 g (3.3 mmol) of (S)-4-(2,2-dimethoxy-ethylamino)-3-hydroxy-butyric acid methyl ester in 6.5 ml of DMF. The solution was stirred and warmed up over night. The reaction was poured on aqueous 10% KHSO4/EtOAc (3×). The organic phases were washed with aqueous 10% KHSO4, saturated NaHCO3, 10% NaCl and dried over Na2SO4 to yield 1.91 g (62%) of the titled compound as light brown oil. MS: 469.14 (MH+).

Workup

  1. temperaturewarmed up over night
  2. washThe organic phases were washed with aqueous 10% KHSO4, saturated NaHCO3, 10% NaCl
  3. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-847ad5d29e724b66a2d1373af0984c8e
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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