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

HRID 456903Notes

Reaction equation

HRID 456903 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×

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 wanned to 23° C. and stirred for 1 hour. 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: δ 7.37–7.25 (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 (brd, 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. customwas wanned to 23° C.
  2. customExcess borane was carefully quenched with water
  3. customThe mixture was then partitioned between a 1:1 mixture of saturated sodium carbonate solution and brine (300 mL) and ethyl acetate (300 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (100% hexane initally

Sources & evidence

ORD record
ord-e4fb8d6e31764de19dde65946f4d1524
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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