Benzyl chloroformate → HCID 66772704, compound

HRID 1966855Notes

Reaction equation

HRID 1966855 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH:10]([NH2:15])[C:9]=2[CH:8]=[N:7]1)[CH3:2].Cl[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19]>C(=O)([O-])[O-].[Na+].[Na+]>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH:10]([NH:15][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[C:9]=2[CH:8]=[N:7]1)[CH3:2]

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 59152911HCID 59152911, compound

Product 1

HCID 66772704HCID 66772704, compoundYield 98.2%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Procedure

To a solution of (4-amino-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (60 mg, 0.27 mmol) in 5% sodium carbonate (0.57 mL) and 1,4-1,4-dioxane (1 mL) was added benzyl chloroformate (58 uL, 0.40 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature slowly, and stirred overnight. The reaction mixture was partitioned between water (10 mL) and dichloromethane (20 mL×3). The combined organic layers were collected and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (50% ethyl acetate in hexanes) to afford racemic (4-benzyloxycarbonylamino-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (94.2 mg, 98.2%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (s, 1 H), 7.49-7.35 (m, 4 H), 5.18 (s, 2 H), 5.23 (s, 2 H), 4.92-4.80 (m, 3 H), 4.23 (dd, J=7.2 Hz, 2 H), 2.52 (m, 2 H), 2.05-1.88 (m, 4 H), 1.30 (t, J=7.2 Hz, 3 H). MS calcd. for C19H23N3O4 357, obsd. (ESI+) [(M+H)+] 358. The chrial separation (Gilson instrument: column: AS-H; flow rate: 15 mL/min; gradient: 55% hexane in propan-2-ol) gave ((R)-4-benzyloxycarbonylamino-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (retention time 7.2 minutes) and ((S)-4-benzyloxycarbonylamino-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (retention time 8.7 minutes). The recovery for both isomers together was 70%.

Workup

  1. customThe reaction mixture was partitioned between water (10 mL) and dichloromethane (20 mL×3)
  2. customThe combined organic layers were collected
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-92238e23652045fc9b3c58cac238f3f6
Source dataset
uspto-grants-2013_04
Patent number
US08420675B2

Reaction notes

Loading…