Lithium borohydride → (3S,4S)-tert-Butyl 3,4-bis(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 1158345Notes

Reaction equation

HRID 1158345 reaction equation
C([O:3][C:4]([C@H:6]1[C@H:10]([C:11](OCC)=[O:12])[CH2:9][N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7]1)=O)C.[Li+].[BH4-]>C1COCC1>[C:19]([O:18][C:16]([N:8]1[CH2:7][C@@H:6]([CH2:4][OH:3])[C@H:10]([CH2:11][OH:12])[CH2:9]1)=[O:17])([CH3:22])([CH3:21])[CH3:20]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 59512444(3R,4R)-1-tert-butyl 3,4-diethyl pyrrolidine-1,3,4-tricarboxylate

Product 1

HCID 59512458(3S,4S)-tert-Butyl 3,4-bis(hydroxymethyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a ice-cooled solution of (3S*,4S*)-pyrrolidine-1,3,4-tricarboxylic acid 1-tert-butyl ester 3,4-diethyl ester (36 g, 114.15 mmol) in THF (1 L), is added dropwise a solution of LiBH4 (228.3 mmol) in THF (250 mL). The reaction mixture is stirred overnight at room temperature and quenched with an aqueous solution of NaOH 2N (400 mL). Ether is added, the layers are separated and the aqueous one back extracted twice with ether. The combined organic extracts are dried over Na2SO4, filtered and concentrated to give the title compound which is used without further purification in the next step. TLC, Rf (CH2Cl2/MeOH 95:5)=0.14. MS (LC-MS): 232.2 [M+H]+; tR (HPLC, C18 column, 5-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.37 min.

Workup

  1. customquenched with an aqueous solution of NaOH 2N (400 mL)
  2. additionEther is added
  3. customthe layers are separated
  4. extractionthe aqueous one back extracted twice with ether
  5. dry with materialThe combined organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9cc37dde824f44c1bad7465d81a8551e
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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