Tetrahydrofuran → HCID 86689152, compound

HRID 1752468Notes

Reaction equation

HRID 1752468 reaction equation
[NH2:1][C@@:2]([C:12]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]([Br:19])[N:13]=1)([CH2:8][CH2:9][O:10][CH3:11])[C:3]([F:7])([F:6])[CH2:4][OH:5].[N+:20]([C:23]1[CH:33]=[CH:32]C=C[C:24]=1[C:25](N=C=S)=O)([O-:22])=[O:21].C1CCC(N=C=NC2CCCCC2)CC1.C([N:51]([CH2:54]C)[CH2:52][CH3:53])C.C1C[O:59]CC1>>[Br:19][C:14]1[N:13]=[C:12]([C@:2]2([CH2:8][CH2:9][O:10][CH3:11])[C:3]([F:6])([F:7])[CH2:4][O:5][C:54]([NH:51][C:52](=[O:59])[C:53]3[CH:32]=[CH:33][C:23]([N+:20]([O-:22])=[O:21])=[CH:24][CH:25]=3)=[N:1]2)[C:17]([F:18])=[CH:16][CH:15]=1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 10727048Benzoyl isothiocyanate, 2-nitro-HCID 86689151HCID 86689151, compound

Product 1

HCID 86689152HCID 86689152, compoundYield 35.6%

Procedure

To a solution of (R)-3-amino-3-(6-bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-5-methoxy-pentan-1-ol (1.15 g, 3.35 mmol) in THF (27.9 ml) was added nitrobenzoyl-isothiocyanate (767 mg, 3.69 mmol). After stirring at rt for 4 hr DCC (760 mg, 3.69 mmol) and triethylamine (34.1 mg, 0.337 mmol) was added. Stirring was continued at rt for 19 hr and finally, the reaction mixture was kept at 70° C. for 5 h. The yellow-orange solution was cooled and evaporated in vacuo. The crude product (2.7 g) was chromatographed over silica gel (Redisep column 120 g, cyclohexane/ethyl acetate 7:3) to give the title compound as a light yellow foam. 650 mg (35.6% yield).

Workup

  1. additionwas added
  2. waitfinally, the reaction mixture was kept at 70° C. for 5 h
  3. temperatureThe yellow-orange solution was cooled
  4. customevaporated in vacuo
  5. customThe crude product (2.7 g) was chromatographed over silica gel (Redisep column 120 g, cyclohexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-267e28e86fe24c789c0efa5595b4cc33
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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