Sodium triacetoxyborohydride → {2-[3'-(4-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 553483Notes

Reaction equation

HRID 553483 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)=[CH:4][CH:3]=1.[C:20]([O:24][C:25](=[O:31])[N:26]([CH3:30])[CH2:27][CH:28]=O)([CH3:23])([CH3:22])[CH3:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:20]([O:24][C:25](=[O:31])[N:26]([CH2:27][CH2:28][N:17]1[CH2:16][CH2:15][N:14]([C:9]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:13][CH:12]=[CH:11][N:10]=2)[CH2:19][CH2:18]1)[CH3:30])([CH3:23])([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 10725881tert-butyl N-methyl-N-(2-oxoethyl)carbamateHCID 673669592-(4-Fluorophenyl)-3-(piperazin-1-yl)pyrazine

Product 1

HCID 67366867{2-[3'-(4-Fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-carbamic acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (2.5 g, 9.7 mmol, 1 eq.) in 1,2 dichloroethane (20 mL). Add methyl-(2-oxo-ethyl)-carbamic acid tert-butyl ester (1.77 g, 10.19 mmol, 1.05 eq.). Add sodium triacetoxy-borohydride (3.10 g, 14.6 mmol, 1.5 eq.). Stir at room temperature for 18 hr. Partition the reaction mixture between aqueous saturated NaHCO3 and dichloromethane. Separate the layers. Extract the organic layer with dichloromethane (2×100 mL). Combine the organic layers, dry over anhydrous Na2SO4, filter and concentrate. Purify by normal phase chromatography with 30% EtOAc/hexane—100% EtOAc to afford the title preparation (3.8 g, 97% yield). MS (loop): m/z=416.3 [M+H].

Workup

  1. customPartition the reaction mixture between aqueous saturated NaHCO3 and dichloromethane
  2. customSeparate the layers
  3. extractionExtract the organic layer with dichloromethane (2×100 mL)
  4. dry with materialCombine the organic layers, dry over anhydrous Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by normal phase chromatography with 30% EtOAc/hexane—100% EtOAc
  8. customto afford the title
  9. custompreparation (3.8 g, 97% yield)

Sources & evidence

ORD record
ord-bc57a883d1e3446f963f46a2710f6866
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

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