Dichloromethane → HCID 89998812, compound

HRID 2273336Notes

Reaction equation

HRID 2273336 reaction equation
CC(C)N=C=N[CH:6]([CH3:8])[CH3:7].C([O:14][CH2:15][C@@H:16]([C:35]([OH:37])=[O:36])[NH:17][C:18]([O:20][CH2:21][C:22]1[C:34]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2[CH:25]=[CH:24][CH:23]=1)=[O:19])(C)(C)C.[C:38]([CH2:41][CH2:42][C:43]([O:45][CH2:46][C@H:47]1[O:54][C@H:51]([O:52][CH3:53])[C@H:50]([O:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69])[C@@H:49]([O:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])[C@@H:48]1[O:85]CC1C=CC(OC)=CC=1)=[O:44])(O)=[O:39].[CH2:95](Cl)Cl>CN(C1C=CN=CC=1)C>[CH:33]1[C:34]2[CH:22]([CH2:21][O:20][C:18]([NH:17][C@H:16]([C:35]([O:37][C:6]([CH3:7])([CH3:8])[CH3:95])=[O:36])[CH2:15][O:14][C:38](=[O:39])[CH2:41][CH2:42][C:43]([O:45][CH2:46][C@H:47]3[O:54][C@H:51]([O:52][CH3:53])[C@H:50]([O:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69])[C@@H:49]([O:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])[C@@H:48]3[OH:85])=[O:44])=[O:19])[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:29]=2[CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 12734DiisopropylcarbodiimideHCID 57046908HCID 57046908, compoundHCID 89999082HCID 89999082, compound

Product 1

HCID 89998812HCID 89998812, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

DMAP (6.2 mg, 0.05 mmol) and DIC (0.16 mL, 1.01 mmol) were added to a stirred solution of O-tert-butyl-N-fluorenylmethoxycarbonyl-L-serine 9 (0.39 g, 0.60 mmol) in CH2Cl2 (3 ml). After 1 h, the carboxylic acid derivative 22 (0.41 g, 0.50 mmol) was added and the reaction was stirred for 5-9 h until no further conversion of the starting material could be detected by TLC analysis. The reaction mixture was diluted with CH2Cl2 (20 mL), washed with water (2×10 mL) and brine (10 mL). The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate-hexane gradient elution) to afford the title compound 23 (0.47 g, 0.40 mmol) as a colorless amorphous solid in 79% yield. Analytical data for 23: Rf=0.43 (ethyl acetate/hexane, 3/7, v/v); [α]D24+36.1° (c=1.0, CHCl3); 1H NMR (300 MHz, CDCl3): δ, 0.88 (t, 6H, 2×CH3), 1.17 (m, 40H, 20×CH2), 1.38 (s, 9H, t-Bu), 1.54 (m, 4H, 2×CH2), 2.53 (m, 4H, 2×CH2), 3.18 (dd, 1H, J2,3=9.7 Hz, H-2), 3.26 (s, 3H, OCH3), 3.28 (m, 1H, H-4), 3.42-3.66 (m, 5H, H-3, 5, OCH2, OCH2a), 3.67 (s, 3H, OCH3), 3.79 (m, 1H, OCH2b), 4.11-4.46 (m, 8H, H-6a, 6b, ½CH2Ph, Ser-CαH, Ser-CβH2, CH2Fmoc), 4.66 (d, 1H, J1,2=3.3 Hz, H-1), 4.71 (d, 1H, J2=10.5 Hz, ½CH2Ph), 5.71 (d, 1H, JNH,CH=8.1 Hz, Ser-NH), 6.75-7.64 (m, 12H, aromatic) ppm; 13C NMR (75 MHz, CDCl3): δ, 14.2, 22.8, 26.1, 26.4, 28.0, 28.9, 29.5, 29.6, 29.7, 29.8, 30.2, 30.7, 32.0, 47.0, 54.0, 55.2, 55.3, 64.7, 67.3, 68.6, 71.8, 73.8, 74.6, 80.8, 81.8, 83.0, 97.9, 99.7, 113.9, 120.1, 125.2, 125.3, 127.2, 127.8, 129.9, 130.3, 141.4, 142.5, 143.9, 155.9, 159.4, 168.4, 171.7, 172.0, 181.3 ppm; HR FAB MS [M+Na]+ calcd for C69H105NO14Na 1194.7433. found 1194.7433.

Workup

  1. washwashed with water (2×10 mL) and brine (10 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (ethyl acetate-hexane gradient elution)

Sources & evidence

ORD record
ord-8cbc1244d8744f899e7c9c3862cac10a
Source dataset
uspto-grants-2015_09
Patent number
US09120838B2

Reaction notes

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