Sodium Acetate → (1R,3R,4S,5S)-3-[(3,3-Dimethyl-1,3-dihydro-isobenzofuran-5-ylmethyl)-amino]-5-[3-fluoro-4-nitro-5-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzyl]-1-oxo-hexahydro-1lambda*4*-thiopyran-4-ol

HRID 420339Notes

Reaction equation

HRID 420339 reaction equation
[NH2:1][C@@H:2]1[C@@H:7]([OH:8])[C@H:6]([CH2:9][C:10]2[CH:15]=[C:14]([O:16][C@@H:17]([CH3:22])[C:18]([F:21])([F:20])[F:19])[C:13]([N+:23]([O-:25])=[O:24])=[C:12]([F:26])[CH:11]=2)[CH2:5][S@@:4](=[O:27])[CH2:3]1.[CH3:28][C:29]1([CH3:40])[C:37]2[C:32](=[CH:33][CH:34]=[C:35]([CH:38]=O)[CH:36]=2)[CH2:31][O:30]1.CC([O-])=O.[Na+].[BH3-]C#N.[Na+]>>[CH3:28][C:29]1([CH3:40])[C:37]2[C:32](=[CH:33][CH:34]=[C:35]([CH2:38][NH:1][C@@H:2]3[C@@H:7]([OH:8])[C@H:6]([CH2:9][C:10]4[CH:15]=[C:14]([O:16][C@@H:17]([CH3:22])[C:18]([F:21])([F:19])[F:20])[C:13]([N+:23]([O-:25])=[O:24])=[C:12]([F:26])[CH:11]=4)[CH2:5][S@@:4](=[O:27])[CH2:3]3)[CH:36]=2)[CH2:31][O:30]1

Participants

5

Reactant 4

HCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 66649569(1R,3R,4S,5S)-3-Amino-5-[3-fluoro-4-nitro-5-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-olHCID 866395423,3-Dimethyl-1,3-dihydroisobenzofuran-5-carbaldehyde

Product 1

HCID 131729392(1R,3R,4S,5S)-3-[(3,3-Dimethyl-1,3-dihydro-isobenzofuran-5-ylmethyl)-amino]-5-[3-fluoro-4-nitro-5-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzyl]-1-oxo-hexahydro-1lambda*4*-thiopyran-4-ol

Procedure

The title compound was prepared in an analogous manner as described for example 1h, starting from (1R,3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-ol (0.075 g, 0.19 mmol), 3,3-dimethyl-1,3-dihydro-isobenzofuran-5-carbaldehyde (0.036 g, 0.203 mmol), NaOAc (0.032 g, 0.38 mmol) and NaBH3CN (0.013 g, 0.19 mmol) and was obtained as a light yellow foam after chromatographic purification on silica gel: TLC (EtOAc-MeOH 19:1) Rf=0.20; HPLC RtA=1.78 min; ESIMS [M+H]+=575; 1H NMR (400 MHz, CDCl3): δ 7.19 (m, 2H), 7.04 (s, 1H), 6.84 (s, 1H), 6.78 (d, 1H), 5.04 (s, 2H), 4.76 (m, 1H), 4.25 (s broad, 1H), 3.94 (d, 1H), 3.76 (d, 1H), 3.53 (ddd, 1H), 3.37 (ddd, 1H), 2.8-3.15 (m, 5H), 2.14 (m, 2H), 1.52 (d, 3H), 1.48 (s, 6H).

Workup

  1. customwas obtained as a light yellow foam
  2. customafter chromatographic purification on silica gel
  3. customHPLC RtA=1.78 min

Sources & evidence

ORD record
ord-a0843571c71740f88c2ddb0fa843f627
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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