Benzoyl isothiocyanate → HCID 89573589, compound

HRID 1911012Notes

Reaction equation

HRID 1911012 reaction equation
[NH2:1][C@:2]1([CH3:15])[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[O:5][CH2:4][C@@H:3]1[CH2:13][OH:14].[C:16]([N:24]=[C:25]=[S:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[F:12][C:8]1[CH:7]=[C:6]2[C:11]([C@:2]([NH:1][C:25]([NH:24][C:16](=[O:23])[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[S:26])([CH3:15])[C@@H:3]([CH2:13][OH:14])[CH2:4][O:5]2)=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 71060828HCID 71060828, compound

Product 1

HCID 89573589HCID 89573589, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ((3S,4S)-4-amino-7-fluoro-4-methylchroman-3-yl)methanol from step F3 (795 mg, 3.76 mmol), and benzoyl isothiocyanate (614 mg, 3.76 mmol) in THF (50 mL) was stirred at rt for 1.5 h. The resulting mixture was concentrated in vacuo. The crude residue was purified using silica gel column chromatography (95:5 chloroform/MeOH) to afford rel-N-(((3S,4S)-7-fluoro-3-(hydroxymethyl)-4-methylchroman-4-yl)carbamothioyl)benzamide (1.32 g, 3.53 mmol, 94% yield). LCMS (M+Na)+=397.2. 1H NMR (500 MHz, DMSO-d6) δ 11.45 (s, 1H), 11.26 (s, 1H), 7.91 (dd, J=8.4, 1.2 Hz, 2H), 7.68-7.58 (m, 1H), 7.57-7.41 (m, 3H), 6.86 (td, J=8.5, 2.7 Hz, 1H), 6.70 (dd, J=10.4, 2.7 Hz, 1H), 4.84 (t, J=4.7 Hz, 1H), 4.56 (dd, J=11.4, 3.1 Hz, 1H), 4.20 (dd, J=11.4, 1.6 Hz, 1H), 3.64-3.52 (m, 1H), 3.26-3.12 (m, 2H), 2.07 (s, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. customThe crude residue was purified

Sources & evidence

ORD record
ord-32656d191a0146208f7fb810aad60472
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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