3,4-Dichlorobenzaldehyde → HCID 103662939, compound

HRID 2281011Notes

Reaction equation

HRID 2281011 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH:18]=O.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18][NH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1

Participants

6

Reactant 3

HCID 227103,4-DichlorobenzaldehydeHCID 27563701-Boc-3-aminopyrrolidineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 103662939HCID 103662939, compoundYield 88.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of tert-butyl 3-aminopyrrolidine-1-carboxylate (1.5 g; 8.05 mmol; 1.00 eq and 3,4-dichlorobenzaldehyde (1339.00 mg; 7.65 mmol; 0.95 eq.) in methanol (10.00 ml) and acetic acid (1.00 ml) was stirred for 30 minutes at ambient temperature, then sodium cyanoborohydride (9.66 ml; 9.66 mmol; 1.20 eq.) was added. The reaction mixture was stirred for an additional 12 hours at ambient temperature at which time the reaction was quenched by pouring into aqueous ammonia (30 mL). The resulting inorganic precipitate was filtered off, and washed with dichloromethane (50 mL). The organic layer was separated and the remaining aqueous layer was extracted with dichloromethane (50 mL×3). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The resultant oil is purified under flash chromatography using silicon column with gradient of ethyl acetate in hexanes to afford the desired intermediate, tert-Butyl 3-((3,4-dichlorobenzyl)amino)pyrrolidine-1-carboxylate (2.47 g; 7.16 mmol; 88.9%), as a clear viscous oil. LC-MS (M+H=346, obsd.=288 (M-57))

Workup

  1. customwas quenched
  2. additionby pouring into aqueous ammonia (30 mL)
  3. filtrationThe resulting inorganic precipitate was filtered off
  4. washwashed with dichloromethane (50 mL)
  5. customThe organic layer was separated
  6. extractionthe remaining aqueous layer was extracted with dichloromethane (50 mL×3)
  7. washThe combined organic extracts were washed with brine (50 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resultant oil is purified under flash chromatography

Sources & evidence

ORD record
ord-075c68dee57b47e2ad0c78cb75a83d39
Source dataset
uspto-grants-2015_09
Patent number
US09139568B2

Reaction notes

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