Lithium borohydride → benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidine-1-carboxylate

HRID 2308094Notes

Reaction equation

HRID 2308094 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([O:10][CH3:11])[CH2:7][N:6]1[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=O.[Li+].[BH4-]>C1COCC1>[CH2:15]([O:14][C:12]([N:6]1[CH2:7][C@H:8]([O:10][CH3:11])[CH2:9][C@H:5]1[CH2:3][OH:2])=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 14036171(2S, 4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester

Product 1

HCID 59971156benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 5 mL of anhydrous THF was added 1.50 g (5.62 mmol) of (2S,4R)-4-Methoxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester and the mix was cooled to 0° C. To reaction mixture was added 3.34 mL of LiBH4 (2.0 M in THF) drop-wise over 5 min and was then stirred for 2 h. The mixture was quenched with 1 mL of Sat. NaHCO3, diluted with 50 mL of EtOAc and washed with Sat. NaHCO3 (2×50 mL). The organic layer was dried over NaSO4 and concentrated to give an amber oil. Purification was accomplished through 50 mL of silica eluting with EtOAc/CH2Cl2 (7:3). The pure factions were combined, concentrated and subsequently put on the high vacuum for 24 h to give 1.3 g (92%) of (2S, 4R)-2-Hydroxymethyl-4-methoxy-pyrrolidine-1-carboxylic acid benzyl ester as clear oil. HPLC: Rt 3.41 min. (100% area). 1H NMR (CDCl3, 300 MHz) δ; 7.51-7.38 (5H, m), 5.24-5.00 (2H, m), 4.45-4.40 (1H, m), 4.23-4.18 (1H, m), 3.95-3.73 (3H, m), 3.51-3.42 (1H, m), 3.31 (3H, s), 2.22-2.14 (1H, m). LCMS (APCI) (M+H+) m/z: 266.2.

Workup

  1. customTo reaction mixture
  2. customThe mixture was quenched with 1 mL of Sat. NaHCO3
  3. additiondiluted with 50 mL of EtOAc
  4. washwashed with Sat. NaHCO3 (2×50 mL)
  5. dry with materialThe organic layer was dried over NaSO4
  6. concentrationconcentrated
  7. customto give an amber oil
  8. customPurification
  9. concentrationconcentrated
  10. waitsubsequently put on the high vacuum for 24 h

Sources & evidence

ORD record
ord-23e9aa5a2c084084a537431d6d0d01f1
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

Loading…