tert-Butyl Formate → {(3R,4S,5S)-5-[3-Fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester

HRID 420318

반응식

HRID 420318 반응식
[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([F:22])[C:19]([N+:23]([O-:25])=[O:24])=[C:18](F)[CH:17]=2)[CH2:11][S:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]([F:36])([F:35])[C@H:30]([OH:34])[CH2:31][O:32][CH3:33].C(O[K])(C)(C)C.C(OC(C)(C)C)=O>C1COCC1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:17]=[C:18]([O:34][C@H:30]([CH2:31][O:32][CH3:33])[C:29]([F:36])([F:35])[F:28])[C:19]([N+:23]([O-:25])=[O:24])=[C:20]([F:22])[CH:21]=2)[CH2:11][S:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]

참가 물질

7

반응물 4

HCID 61207tert-Butyl FormateHCID 57386308[(3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl esterHCID 866395431204343-96-3HCID 178418922HCID 178418922, 화합물

생성물 1

HCID 66649544{(3R,4S,5S)-5-[3-Fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of [(3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1 g, 2.47 mmol) and (R)-1,1,1-trifluoro-3-methoxy-propan-2-ol (392 mg, 2.72 mmol) in THF (13 mL) was added tert-BuOK (277 mg, 2.47 mmol) in small portions at 0° C. over a period of 30 min. After 1 h the cooling bath was removed and the orange solution was stirred at room temperature for 5 h. The reaction mixture was diluted with EtOAc (500 mL) and washed with ice cooled K2CO3 solution and cold brine. The organic phase was dried over Na2SO4, filtered and evaporated to yield a brown-yellowish foam: TLC Rf=0.50 (toluene-ETA 85:15); HPLC RtE=1.157 min; ESIMS [M+H-Boc]+=429; 1H NMR (600 MHz, DMSO-d6): δ 7.28 (s, 1H), 7.10 (d, 1H), 6.71 (d, 1H), 5.65 (broad, 1H), 4.95 (d, 1H), 3.83 (dd, 1H), 3.73 (dd, 1H), 3.42 (m, 1H), 3.31 (s, 3H), 3.25 (dd, 1H), 2.93 (m, 1H), 2.54 (d, 1H), 2.48-2.35 (m, 2H), 2.32-2.20 (m, 2H), 1.94 (m, 1H), 1.37 (s, 9H).

후처리

  1. customAfter 1 h the cooling bath was removed
  2. additionThe reaction mixture was diluted with EtOAc (500 mL)
  3. washwashed with ice
  4. temperaturecooled K2CO3 solution and cold brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a brown-yellowish foam
  9. customHPLC RtE=1.157 min

출처 및 근거

ORD 기록
ord-2c76eaebf9314f3f950f4a41cdbeb8a5
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093406B2

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