Sodium borohydride → HCID 178464724, compound

HRID 709859Notes

Reaction equation

HRID 709859 reaction equation
C([O:3][C:4](=O)[C:5]([NH2:28])([C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][C@H:18]3[CH2:23][CH2:22][C@H:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19]3)[CH:13]=2)[N:8]=1)[CH3:6])C.[BH4-].[Na+]>CO.O1CCCC1>[NH2:28][C:5]([C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][C@H:18]3[CH2:19][CH2:20][C@H:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:22][CH2:23]3)[CH:13]=2)[N:8]=1)([CH3:6])[CH2:4][OH:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydride2×HCID 178471902HCID 178471902, compound

Product 1

HCID 178464724HCID 178464724, compoundYield 50.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-quinolin-2-yl]-propionic acid ethyl ester (18 mg as TFA salt, 0.000035 mol) was dissolved in a mixture of methanol (2.0 mL, Acros) and tetrahydrofuran (2.0 mL, Acros), then sodium tetrahydroborate (3.8 mg, 0.00010 mol, Aldrich) was added. After 2 h, additional sodium tetrahydroborate (8.1 mg, 0.00021 mol, Aldrich) was added. After an additional 2 h, the reaction mixture was quenched with 250 uL of to saturated NH4Cl, and solvents were removed under vacuum. DMSO (½ mL) was added to the residue but it did not completely solubilize. The material was partitioned between methylene chloride and water. The emulsion was broken up by adding saturated sodium chloride and solid sodium chloride. The organics were dried with magnesium sulfate, filtered and evaporated. The residue was purified via preparative HPLC to give pure product (6.3 mg, 38%) as TFA salt. MS: m/z=357.20 [M+H]+. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm: 8.19 (d, J=8.5 Hz, 1H), 7.96 (d, J=9.3 Hz, 1H), 7.39-7.46 (m, 2H), 7.13 (d, J=2.8 Hz, 1H), 4.24-4.36 (m, 1H), 4.12-4.21 (m, 2H), 2.23-2.32 (m, 2H), 1.88-1.96 (m, 2H), 1.78 (s, 3H), 1.41-1.54 (m, 2H), 1.10-1.27 (m, 3H), 0.91 (s, 9H).

Workup

  1. waitAfter an additional 2 h
  2. customthe reaction mixture was quenched with 250 uL of to saturated NH4Cl, and solvents
  3. customwere removed under vacuum
  4. additionDMSO (½ mL) was added to the residue but it
  5. customThe material was partitioned between methylene chloride and water
  6. additionby adding saturated sodium chloride and solid sodium chloride
  7. dry with materialThe organics were dried with magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified via preparative HPLC

Sources & evidence

ORD record
ord-f670011974684db0afac785a79be7b38
Source dataset
uspto-grants-2015_11
Patent number
US09181191B2

Reaction notes

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