(2S,4R)-1-[(benzyloxy)carbonyl]-4-methoxypyrrolidine-2-carboxylic acid → benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidine-1-carboxylate

HRID 381758Notes

Reaction equation

HRID 381758 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][CH3:17])[CH2:13][C@H:12]1[C:18](O)=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1>[OH:19][CH2:18][C@@H:12]1[CH2:13][C@@H:14]([O:16][CH3:17])[CH2:15][N:11]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

3

Reactant 1

HCID 12849521(2S,4R)-1-[(benzyloxy)carbonyl]-4-methoxypyrrolidine-2-carboxylic acid

Product 1

HCID 59971156benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

A solution of borane-tetrahydrofuran complex in THF (1M, 53.0 mL, 53.0 mmol, 3.50 equiv) was added to a solution of (2S,4R)-1-[(benzyloxy)carbonyl]-4-methoxy-2-pyrrolidinecarboxylic acid (3-2, 4.23 g, 15.1 mmol, 1 equiv) in THF (200 mL) at 0° C. The resulting mixture was warmed to 23° C. and stirred for 1 h. Excess borane was carefully quenched with water. The mixture was then partitioned between a 1:1 mixture of saturated sodium carbonate solution and brine (300 mL) and ethyl acetate (300 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexane initally, grading to 100% EtOAc) to provide benzyl (2S,4R)-2-(hydroxymethyl)-4-methoxy-1-pyrrolidinecarboxylate (3-3) as a colorless oil. 1H NMR (300 MHz, CDCl3) major rotamer: δ7.37-7.25 (br m, 5H), 5.18 (d, 1H, J=12.4 Hz), 5.13 (d, 1H, J=12.2 Hz), 4.51 (dd, 1H, J=8.3,2.2 Hz), 3.86 (m, 1H), 3.78 (dd, 1H, J=11.7, 2.2 Hz), 3.72 (br d, 1H, J=11.7 Hz), 3.61 (ddd, 1H, J=9.8, 7.4, 2.2 Hz), 3.44 (dd, 1H, J=12.2, 4.4 Hz), 3.30 (s, 3H), 2.18 (m, 1H), 1.64 (m, 1H).

Workup

  1. customExcess borane was carefully quenched with water
  2. customThe mixture was then partitioned between a 1:1 mixture of saturated sodium carbonate solution and brine (300 mL) and ethyl acetate (300 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (100% hexane initally

Sources & evidence

ORD record
ord-fb7d40f5e58d4e7396e1e78c918c9755
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

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