Potassium borohydride → HCID 68948772, compound

HRID 332134Notes

Reaction equation

HRID 332134 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH:9]1[CH2:11][C:10]1([C:20](=[O:22])[CH3:21])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[K+]>CO>[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH:9]1[CH2:11][C:10]1([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)[CH:20]([OH:22])[CH3:21])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 4192641Potassium borohydrideHCID 57871291HCID 57871291, compound

Product 1

HCID 68948772HCID 68948772, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(±)-[2-Acetyl-2-(3,4-dichlorophenyl)-cyclopropylmethyl]-carbamic acid tert-butyl ester was added to methanol and stirred at ambient temperature under Ar (g) in a 50 mL round-bottomed flask. Potassium borohydride was added portion wise and the suspension stirred overnight. The resulting suspension partitioned between EtOAc (10 mL) and water (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL), and the combined layers washed with brine (10 mL). The organic layer was dried over sodium sulfate for 2 hours and filtered, concentrated under reduced pressure, and dried for 1 hour to afford 0.523 g of a white sticky solid. The solid was purified on a filter pad of silica eluting with 4/1 hexanes/EtOAc (v/v), switching to 6/4 hexanes/EtOAc (v/v) upon collection of the major spot. The second (other) diastereomer was collected. The desired compound is pale oil; Yield: 0.328 g 49%; The undesired diastereomer is a white solid; Yield: 0.120 g 18%; 1H NMR: Desired diastereomer: (300 MHz, DMSO-d6) δ□ 7.50-53 (m, 2H, J=2.1 Hz, ArH), 7.22-25 (dd, 1H, J=9.0 Hz, dr=1.8 Hz, ArH), 6.91 (bs, 1H, OH), 4.26 (m, 1H, NH), 3.50 (m, 1H, CH2N), 3.32 (m, 1H, CH2N), 3.26 (m, 3H, CH3), 1.40 (s, 9H, tert-Bu), 1.02 (m, 2H, ArCCH2), 0.55 (m, 1H, CHCH2N); Undesired diastereomer (not shown): (300 MHz, CDCl3) (507.57 (m, JEH, ArH), 7.50 (d, 1H, J=8.1 Hz, ArH), 7.31 (dd, 1H, J=8.4 Hz, J=1.8 Hz, ArH), 7.11 (bs, 1H, OH), 4.63 (d, 1H, J=3.3 Hz, NH), 3.46 (m. 1H), 3.33 (s, 3H), 3.12 (m, 2H), 1.38 (s, 9H, tert-Bu), 1.30 (m, 1H), 0.85 (d, 2H, J=6.0 Hz, ArCCH2), 0.78 (m, 1H, CHCH2N)

Workup

  1. customThe resulting suspension partitioned between EtOAc (10 mL) and water (10 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  3. washthe combined layers washed with brine (10 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate for 2 hours
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customdried for 1 hour

Sources & evidence

ORD record
ord-22da7d9f0db84ff7b17eec6c1a40c238
Source dataset
uspto-grants-2014_11
Patent number
US08877798B2

Reaction notes

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