Methanol → tert-butyl (3R)-3-{[3-chloro-5-(hydroxymethyl)-2-pyridinyl]amino}-1-pyrrolidinecarboxylate

HRID 2376116Notes

Reaction equation

HRID 2376116 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[C:34]([Cl:35])=[CH:33][C:27]([C:28](OCC)=[O:29])=[CH:26][N:25]=2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].CO.[Na].[K]>CCCCCC.C1COCC1>[Cl:35][C:34]1[C:24]([NH:23][C@@H:20]2[CH2:21][CH2:22][N:18]([C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[CH2:19]2)=[N:25][CH:26]=[C:27]([CH2:28][OH:29])[CH:33]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 16211683Potassium alloy, nonbase, K,NaHCID 21225700DiisobutylaluminumhydrideHCID 68959254ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate

Product 1

HCID 86603728tert-butyl (3R)-3-{[3-chloro-5-(hydroxymethyl)-2-pyridinyl]amino}-1-pyrrolidinecarboxylateYield 41.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
7.5 °C

Procedure

A solution of diisobutylaluminium hydride in hexane solution (0.93M) (138 ml) was added to dropwise a solution of ethyl 6-{[(3R)-1-(tert-butoxycarbonyl)-3-pyrrolidinyl]amino}-5-chloronicotinate (15.9 g) in THF (200 ml) with stirring at 0-15° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at 5-20° C. for 4 hours. The reaction mixture was cooled at 5° C. and MeOH (10 ml) was added and the reaction mixture was stirred at ambient temperature for 20 minutes. The potassium sodium tatarate tetrahydrate (36.4 g) was added to a above solution and the resultant mixture was stirred at ambient temperature for 2 hours. The reaction mixture was filtrated and the filtrate was dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-n-hexane (9:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give tert-butyl (3R)-3-{[3-chloro-5-(hydroxymethyl)-2-pyridinyl]amino}-1-pyrrolidinecarboxylate (5.85 g).

Workup

  1. stirringthe reaction mixture was stirred at 5-20° C. for 4 hours
  2. temperatureThe reaction mixture was cooled at 5° C.
  3. stirringthe reaction mixture was stirred at ambient temperature for 20 minutes
  4. filtrationThe reaction mixture was filtrated
  5. dry with materialthe filtrate was dried over MgSO4
  6. customThe solvent was evaporated in vacuo
  7. customthe residue was chromatographed on silicagel
  8. washeluting with AcOEt-n-hexane (9:1)
  9. additionThe eluted fractions containing the desired product
  10. customwere collected
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-b5a0964be9f04e1c976e5d18bc6745c8
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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