Acetic Acid → HCID 59400150, compound

HRID 2389538Notes

Reaction equation

HRID 2389538 reaction equation
[OH:1][C@@H:2]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:3]([NH:5][C@H:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][CH2:7]1)=[O:4].[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:15][C@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([OH:1])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:7]2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59400104HCID 59400104, compound

Product 1

HCID 59400150HCID 59400150, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-hydroxy-2-phenyl-N—((S)-1,2,3,4-tetrahydroquinolin-3-yl)acetamide (355 mg, 1.26 mmol) in 1,2-dichloroethane (20 mL) was added 4-fluorobenzaldehyde (160 μL, 1.51 mmol) followed by glacial acetic acid (86 μL) and sodium triacetoxyborohydride (533 mg, 2.51 mmol). The reaction was stirred at room temperature for 16 hours. The reaction was diluted with DCM (20 mL) and quenched by addition of water (20 mL). The organic layer was separated and the aqueous layer was once again extracted with DCM (20 mL). The combined organic extracts were washed with water (2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography using a gradient (20-40% EtOAc in hexanes). The desired product (S)—N—((S)-1-(4-fluorobenzyl)-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamide was obtained as a beige solid (351 mg, 72% yield). 1H NMR (DMSO-d6) 400 MHz δ 7.67 (d, J=7.8 Hz, 1H), 7.39-7.34 (m, 2H), 7.33-7.22 (m, 5H), 7.12-7.07 (m, 2H), 6.96-6.90 (m, 2H), 6.58-6.52 (m, 2H), 6.07 (d, J=5.1 Hz, 1H), 4.91 (d, J=4.7 Hz, 1H), 4.45 (d, J=16.8 Hz, 1H for AB system), 4.41 (d, J=16.4 Hz, 1H for AB system), 4.24-4.15 (m, 1H), 3.34 (ddd, J=11.3, 3.5, 1.2 Hz, 1H), 3.22 (dd, J=11.0, 7.0 Hz, 1H), 2.95 (dd, J=15.7, 4.7 Hz, 1H), 2.80 (dd, J=16.0, 7.8 Hz, 1H). LCMS m/e 391 (M+H).

Workup

  1. customquenched by addition of water (20 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was once again extracted with DCM (20 mL)
  4. washThe combined organic extracts were washed with water (2×50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated to dryness
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-462bb537975a4ace971c4b5815e5a450
Source dataset
uspto-grants-2012_09
Patent number
US08273754B2

Reaction notes

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