Methanol → 3-Cyano-4-(n,n-bis(t-butoxycarbonyl)aminomethyl)benzoic acid

HRID 1839448Notes

Reaction equation

HRID 1839448 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]([O:8]C)=[O:7])#[N:2].CO.[Li+].[OH-]>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][N:14]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C:6]([OH:8])=[O:7])#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 23450331Methyl 3-cyano-4-(n,n-bis(t-butoxycarbonyl)aminomethyl)benzoate

Product 1

HCID 544478313-Cyano-4-(n,n-bis(t-butoxycarbonyl)aminomethyl)benzoic acidYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −25° C. solution of methyl 3-cyano-4-(N,N-bis-(t-butoxycarbonyl)aminomethyl)benzoate (1.81 g, 4.64 mmol) in THF (14 mL) was added a 1:1 mixture of MeOH (4.6 mL) and 1 M LiOH (4.6 mL). After 1.25 h, the reaction was quenched with 1 N HCl (4.6 mL), diluted with Et2O (150 mL) and washed with H2O (2×30 mL). The combined aqueous layers was extracted with EtOAc (150 mL). The combined organic layers was MgSO4 dried, filtered, and concentrated. The crude material was chromatographed (0.5% HOAc in 30% EtOAc/hexanes to 0.5% HOAc in 40% EtOAc/hexanes) to give the title compound (767 mg, 44%); IR(CHCl3): 1146, 1370, 1704, 2984, 3020 cm−1; NMR(300 MHz, DMSO-d6): 1.36 (s, 18H); 4.93 (s, 2H); 7.41 (d, 1H, J=8.4 Hz); 8.21 (d, 1H, J=8.4 Hz); 8.25 (s, 1H); MS(FD): 377.0.

Workup

  1. customthe reaction was quenched with 1 N HCl (4.6 mL)
  2. additiondiluted with Et2O (150 mL)
  3. washwashed with H2O (2×30 mL)
  4. extractionThe combined aqueous layers was extracted with EtOAc (150 mL)
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was chromatographed (0.5% HOAc in 30% EtOAc/hexanes to 0.5% HOAc in 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-17d0d614a95c467c986d3e1d2c71051d
Source dataset
uspto-grants-2004_01
Patent number
US06677369B2

Reaction notes

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