Hydrochloric Acid → HCID 86758397, compound

HRID 1004781Notes

Reaction equation

HRID 1004781 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:21][CH2:20][CH2:19][NH:18][C@H:17]2[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CC1C=CC(S(O)(=O)=O)=CC=1.CN([CH2:45][C:46]1[C:50](C=O)=[N:49][NH:48][N:47]=1)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[B].[OH-].[Na+].[CH3:71][N:72]([CH:74]=O)[CH3:73]>C1(C)C=CC=CC=1>[F:30][C:2]([F:1])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:21][CH2:20][CH2:19][N:18]([CH2:45][C:46]3[N:47]=[N:48][N:49]([CH3:50])[C:74]=3[N:72]([CH3:73])[CH3:71])[C@H:17]2[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 5462311BoronHCID 98818305-[(Dimethylamino)methyl]-2H-1,2,3-triazole-4-carboxaldehydeHCID 115924984-Methylbenzene-1-sulfonic acid--(2R,3S)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)morpholine (1/1)

Product 1

HCID 86758397HCID 86758397, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluorophenyl)morpholine TsOH salt (609 g, 1 mol) and 4-N,N-dimethylaminomethyl-5-formyl-1,2,3-triazole (225 g, 1.5 mol) are suspended in 3L of toluene and 1 L of DMF. The resulting suspension was stirred for 30 minutes, then 1 eq. of sodium triacetoxyborohydride (212 g, 1 mol) was added. After 30 minutes, another portion of sodium triacetoxyborohydride (212g, 1 mol) was added. The resulting solution/suspension was aged at 25° C. for 5 hours and the reaction was completed when starting material secondary amine was less than 0.1 A % (at 220 nm) as judged by LC. When the reaction was completed, 2 eq. of 1N HCl (2 L, 2 mol) was added and the reaction mixture was aged for 4 hours (to break some boron complexes). The solution was then neutralized back to pH=8~9 with NaOH or Na3PO4 and extracted with toluene (3 L) and organic layer was washed twice with water and concentrated to obtain 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)-ethoxy)-4-(5-(dimethylamino)-methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine.

Workup

  1. waitAfter 30 minutes
  2. waitThe resulting solution/suspension was aged at 25° C. for 5 hours
  3. waitthe reaction mixture was aged for 4 hours
  4. extractionextracted with toluene (3 L) and organic layer
  5. washwas washed twice with water
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b85398ee5da44c22a993e870f7a0b23a
Source dataset
uspto-grants-2000_04
Patent number
US06051717

Reaction notes

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