Methyl chloroformate → HCID 86702798, compound

HRID 1425916Notes

Reaction equation

HRID 1425916 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:15]2[CH2:16][CH2:17][C@@H:12]1[CH:13]([C:21](O)=[O:22])[CH:14]2[C:18](O)=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OC)=O.[BH4-].[Na+]>C1COCC1.O>[OH:22][CH2:21][CH:13]1[CH:14]([CH2:18][OH:19])[C@H:15]2[N:11]([C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:10])[C@@H:12]1[CH2:17][CH2:16]2

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 4311764Sodium borohydrideHCID 86702797HCID 86702797, compound

Product 1

HCID 86702798HCID 86702798, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

To a solution of (1R,4S)-7-(benzyloxycarbonyl)-7-azabicyclo[2.2.1]heptane-2,3-dicarboxylic acid (L) (2.33 g, 7.30 mmol) in THF (50 mL) was added N-methylmorpholine (2.00 mL, 18.25 mmol). The mixture was cooled to −25° C. before adding methyl chloroformate (1.41 mL, 18.25 mmol) dropwise. The mixture was stirred at −25° C. for 20 minutes and the solid was removed by filtration. The solution was carefully added to a solution of NaBH4 (1.65 g, 43.80 mmol) in water (100 mL) at 0° C. The mixture was stirred for 1 hour at room temperature. The acetone was removed under vacuum and the aqueous phase was extracted with EtOAc (×3). The combined organic phases were washed with 1 M NaOH, dried over MgSO4 and concentrated under vacuum to give (1R,4S)-benzyl 2,3-bis(hydroxymethyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate (LI) as a colorless oil (1.85 g, 6.35 mmol, 87% yield). 1H NMR (CDCl3) δ ppm 1.40 (brs, 1H), 1.54 (brs, 1H), 1.63 (brs, 2H), 1.81 (brs, 1H), 1.98 (brs, 1H), 3.50-3.56 (m, 1H), 3.58-3.67 (m, 2H), 3.69-3.78 (m, 1H), 4.10 (brs, 2H), 5.09 (brs, 2H), 7.34 (brs, 5H); ESIMS found for C16H21NO4 m/z 292 (M+H).

Workup

  1. customthe solid was removed by filtration
  2. stirringThe mixture was stirred for 1 hour at room temperature
  3. customThe acetone was removed under vacuum
  4. extractionthe aqueous phase was extracted with EtOAc (×3)
  5. washThe combined organic phases were washed with 1 M NaOH
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5ef0fdca32fe4220a00b856921e2044c
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

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