Ammonium Chloride → HCID 90308594, compound

HRID 627664Notes

Reaction equation

HRID 627664 reaction equation
[C:1]([O:5][C:6](=[O:39])[N:7]([C:15]1[C:16]([CH3:38])([CH3:37])[S:17](=[O:36])(=[O:35])[CH2:18][C@:19]([C:22]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=2[CH2:31][CH2:32][CH2:33]I)([CH3:21])[N:20]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(#N)C.C(=O)=O.[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6](=[O:39])[N:7]([C:15]1[C:16]([CH3:38])([CH3:37])[S:17](=[O:36])(=[O:35])[C@H:18]2[CH2:33][CH2:32][CH2:31][C:23]3[CH:24]=[CH:25][C:26]([N+:28]([O-:30])=[O:29])=[CH:27][C:22]=3[C@@:19]2([CH3:21])[N:20]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 86587134Acetonitrile dry iceHCID 90301449HCID 90301449, compound

Product 1

HCID 90308594HCID 90308594, compoundYield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of (R)-tert-butyl-N-(5-(2-(3-iodopropyl)-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)-N-tert-butoxycarbonyl-carbamate (172 mg, 0.253 mmol) in THF (2.5 ml) was cooled down to −78° C. and lithium bis(trimethylsilyl)amide (1M solution in THF) (0.40 ml, 0.40 mmol) was added dropwise. The bright yellow mixture was stirred at −78° C. for 20 min, then transferred to −45° C. bath (acetonitrile-dry ice) and stirred for extra 5 min. Saturated NH4Cl (2 ml) solution was added, the mixture was removed from the bath and allowed to reach rt, diluted with EtOAc (5 ml) and water to dissolve solids. Organic layer was washed with brine and concentrated. The residue was purified by FC on 12 g RediSep column using 20-70% EtOAc in heptane to afford tert-butyl-N-((4aS,11bR)-10-nitro-3,3,11b-trimethyl-4,4-dioxido-3,4a,5,6,7,11b-hexahydrobenzo[3,4]cyclohepta[1,2-b][1,4]thiazin-2-yl)-N-tert-butoxycarbonyl-carbamate (105 mg, 0.190 mmol, 75% yield) as white solid. LC/MS (ESI+) m/z=574 (M+Na).

Workup

  1. customtransferred to −45° C.
  2. stirringstirred for extra 5 min
  3. customthe mixture was removed from the bath
  4. customto reach rt
  5. additiondiluted with EtOAc (5 ml) and water
  6. dissolutionto dissolve solids
  7. washOrganic layer was washed with brine
  8. concentrationconcentrated
  9. customThe residue was purified by FC on 12 g RediSep column

Sources & evidence

ORD record
ord-21959c8d4b2c458ca79dff9a2237dfb7
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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