tert-Butyl Formate → (1R,4S)-4-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopent-2-ene-1-carboxylic acid

HRID 1261701Notes

Reaction equation

HRID 1261701 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([C@H:18]2[CH2:22][CH2:21][O:20][CH2:19]2)([C:14]([O:16]C)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+].C(OC(C)(C)C)=O>O1CCCC1.CO.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([C@H:18]2[CH2:22][CH2:21][O:20][CH2:19]2)([C:14]([OH:16])=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 61207tert-Butyl FormateHCID 168937Lithium hydroxide, monohydrateHCID 68930507Methyl(1R,4S)-4-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopent-2-ene-1-carboxylate

Product 1

HCID 68596726(1R,4S)-4-[(tert-Butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopent-2-ene-1-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl (1R,4S)-4-[(tert-butoxycarbonyl)amino]-1-[(3R)-tetrahydrofuran-3-yl]cyclopent-2-ene-1-carboxylate (1.60 g, 5.14 mmol) in tetrahydrofuran (27.8 mL), methanol (27.8 mL) and water (6.0 mL) was added lithium hydroxide monohydrate g, 8.25 mmol). The pink mixture was heated to reflux for 18 h. The organic solvents were removed in vacuo and the aqueous layer was extracted once with ether and then acidified slowly with 6 M HCl until the pH reached 3-4. The resulting suspension was extracted with CH2Cl2 three times. The combined organic layers were dried over MgSO4, filtered and concentrated to give the product as a mixture of two cis/trans isomers (1.59 g) as a light yellow solid. MS calculated for C15H24NO5: (M+H) 298.2; found 198.2 (M+H-Boc).

Workup

  1. temperatureThe pink mixture was heated
  2. temperatureto reflux for 18 h
  3. customThe organic solvents were removed in vacuo
  4. extractionthe aqueous layer was extracted once with ether
  5. extractionThe resulting suspension was extracted with CH2Cl2 three times
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the product
  10. additionas a mixture of two cis/trans isomers (1.59 g) as a light yellow solid

Sources & evidence

ORD record
ord-bdfd8dc1a91744be8ccfec097c1e3124
Source dataset
uspto-grants-2013_06
Patent number
US08470827B2

Reaction notes

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