Toluene → HCID 178477537, compound

HRID 474103Notes

Reaction equation

HRID 474103 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20][C:21]1[N:26]=[C:25]([C@@:27](O)([CH3:42])[CH2:28][NH:29][S:30]([C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)(=[O:32])=[O:31])[C:24]([F:44])=[C:23]([Si:45]([CH2:50][CH3:51])([CH2:48][CH3:49])[CH2:46][CH3:47])[CH:22]=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>C1COCC1>[Br:20][C:21]1[N:26]=[C:25]([C:27]2([CH3:42])[CH2:28][N@@:29]2[S:30]([C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)(=[O:32])=[O:31])[C:24]([F:44])=[C:23]([Si:45]([CH2:50][CH3:51])([CH2:48][CH3:49])[CH2:46][CH3:47])[CH:22]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 86668073(R)-N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamide

Product 1

HCID 178477537HCID 178477537, compoundYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of triphenylphosphine (21.55 g, 82 mmol) and (R)—N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamide (37.56 g, 69 mmol) in 510 ml THF was cooled to 4° C. A solution of diethyl azodicarboxylate in toluene (40% by weight, 38.8 g, 89 mmol) was added in a dropwise while maintaining the temperature below 10° C. The cooling bath was removed and the rm was stirred at rt for 1 h. The reaction mixture was diluted with approx. 1000 ml toluene and THF was removed by evaporation at the rotavap. The resulting toluene solution of crude product was pre-purified on a silca gel column by eluting with hexanes/5-17% EtOAc. Purest fractions were combined, evaporated and crystallized from TBME/hexane to yield 29.2 g of the title compound as white crystals. HPLC: RtH11=2.546 min; ESIMS: 530, 532 [(M+H)+, 1 Br]; 1H-NMR (400 MHz, CDCl3): 8.40 (d, 2H), 8.19 (d, 2H), 7.39 (d, 1H), 3.14 (s, 1H), 3.02 (s, 1H), 2.01 (s, 3H) 1.03-0.83 (m, 15H); α[D]-35.7° (c=0.97, DCM).

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. customThe cooling bath was removed
  3. additionThe reaction mixture was diluted with approx. 1000 ml toluene and THF
  4. customwas removed by evaporation at the rotavap
  5. customThe resulting toluene solution of crude product was pre-purified on a silca gel column
  6. washby eluting with hexanes/5-17% EtOAc
  7. customevaporated
  8. customcrystallized from TBME/hexane

Sources & evidence

ORD record
ord-9846bd3fbd564261b69dbac3c205bcb8
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

Loading…