HCID 59378880, compound → HCID 59378892, compound

HRID 1643912Notes

Reaction equation

HRID 1643912 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-37d75bfee46d4c1a98d1f24d579d5125
Source dataset
uspto-grants-2012_02
Patent number
US08119842B2

Reaction notes

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