HCID 59378880, compound → HCID 59378892, compound

HRID 2201629Notes

Reaction equation

HRID 2201629 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=[C:6]2[C:11]=1[C:10]([C:12]([NH2:14])=[O:13])=[CH:9][CH2:8][CH2:7]2>CO>[F:1][C:2]1[CH:3]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=[C:6]2[C:11]=1[C@H:10]([C:12]([NH2:14])=[O:13])[CH2:9][CH2:8][CH2:7]2

Participants

3

Reactant 1

HCID 59378880HCID 59378880, compound

Product 1

HCID 59378892HCID 59378892, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A suspension of 8-fluoro-6-phenylsulfanyl-3,4-dihydro-naphthalene-1-carboxylic acid amide (1.46 kg) in methanol (23.2 kg) and [Ru(OAc)2((S)-MeOBIPHEP)] (1.83 g) in methanol (1.5 liters) were combined and subjected to hydrogenation at 40° C. and 150 psig (10.3 bar). Completion of the reaction to form (R)-8-fluoro-6-phenylsulfanyl-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid amide (not isolated) was monitored by HPLC. The resulting reaction solution was distilled and the solvent exchanged from methanol to THF (7.6 kg). Analysis of an aliquot of the THF solution provided the following data: MP=167.4-168.2° C.; MS (M+1)=302; H1 NMR (300 MHz): δ(DMSO): 1.56-1.84 (2H, m), 1.91 (2H, m), 2.66 (2H, m), 3.67 (1H, t, J=5.65 Hz), 6.80 (1H, dd, J=1.88, 10.17 Hz), 6.88 (1H, bs, NH), 6.92 (1H, m), 7.32-7.44 (6H, m, Phenyl, NH): [α]D=30.5° (MeOH). Chiral Assay (Area Norm): Column: ChiralCel OD-H (250×4.6 mm), mobile phase 85/15 hexane/ethanol(isocratic) Flow rate 0.7 ml/min, 25° C., uv @230 nm.: (R)-isomer 99.32/(S)-isomer 0.68.

Workup

  1. customsubjected to hydrogenation at 40° C.
  2. customCompletion of the reaction

Sources & evidence

ORD record
ord-88e961aa363c41c2b8e0738e8f00ef57
Source dataset
uspto-grants-2016_06
Patent number
US09365494B2

Reaction notes

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